Unknown Linkage Research Articles

High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

Bioinformatic Identification and Expression Analyses of the MAPK-MAP4K Gene Family Reveal a Putative Functional MAP4K10-MAP3K7/8-MAP2K1/11-MAPK3/6 Cascade in Wheat (Triticum aestivum L.).

The mitogen-activated protein kinase (MAPK) cascades act as crucial signaling modules that regulate plant growth and development, response to biotic/abiotic stresses, and plant immunity. MAP3Ks can be activated through MAP4K phosphorylation in non-plant systems, but this has not been reported in plants to date. Here, we identified a total of 234 putative TaMAPK family members in wheat (Triticum aestivum L.). They included 48 MAPKs, 17 MAP2Ks, 144 MAP3Ks, and 25 MAP4Ks. We conducted systematic analyses of the evolution, domain conservation, interaction networks, and expression profiles of these TaMAPK-TaMAP4K (representing TaMAPK, TaMAP2K, TaMAP3K, and TaMAP4K) kinase family members. The 234 TaMAPK-TaMAP4Ks are distributed on 21 chromosomes and one unknown linkage group (Un). Notably, 25 of these TaMAP4K family members possessed the conserved motifs of MAP4K genes, including glycine-rich motif, invariant lysine (K) motif, HRD motif, DFG motif, and signature motif. TaMAPK3 and 6, and TaMAP4K10/24 were shown to be strongly expressed not only throughout the growth and development stages but also in response to drought or heat stress. The bioinformatics analyses and qRT-PCR results suggested that wheat may activate the MAP4K10-MEKK7-MAP2K11-MAPK6 pathway to increase drought resistance in wheat, and the MAP4K10-MAP3K8-MAP2K1/11-MAPK3 pathway may be involved in plant growth. In general, our work identified members of the MAPK-MAP4K cascade in wheat and profiled their potential roles during their response to abiotic stresses and plant growth based on their expression pattern. The characterized cascades might be good candidates for future crop improvement and molecular breeding.

Rhizosheath drought responsiveness is variety-specific and a key component of belowground plant adaptation.

Biophysicochemical rhizosheath properties play a vital role in plant drought adaptation. However, their integration into the framework of plant drought response is hampered by incomplete mechanistic understanding of their drought responsiveness and unknown linkage to intraspecific plant-soil drought reactions. Thirty-eight Zea mays varieties were grown under well-watered and drought conditions to assess the drought responsiveness of rhizosheath properties, such as soil aggregation, rhizosheath mass, net-rhizodeposition, and soil organic carbon distribution. Additionally, explanatory traits, including functional plant trait adaptations and changes in soil enzyme activities, were measured. Drought restricted soil structure formation in the rhizosheath and shifted plant-carbonfrom litter-derived organic matter in macroaggregates to microbially processed compounds in microaggregates. Variety-specific functional trait modifications determined variations in rhizosheath drought responsiveness. Drought responses of the plant-soil system ranged among varieties from maintaining plant-microbial interactions in the rhizosheath through accumulation of rhizodeposits, to preserving rhizosheath soil structure while increasing soil exploration through enhanced root elongation. Drought-induced alterations at the root-soil interface may hold crucial implications for ecosystem resilience in a changing climate. Our findings highlight that rhizosheath soil properties are an intrinsic component of plant drought response, emphasizing the need for a holistic concept of plant-soil systems in future research on plant drought adaptation.

Impaired Efferocytosis Enables Apoptotic Osteoblasts to Escape Osteoimmune Surveillance During Aging.

Macrophage efferocytosis of apoptotic osteoblasts (apoOBs) is a key osteoimmune process for bone homeostasis. However, apoOBs frequently accumulate in aged bone marrow, where they may mount proinflammatory responses and progressive bone loss. The reason why apoOBs are not cleared during aging remains unclear. In this study, it is demonstrated that aged apoOBs upregulate the immune checkpoint molecule CD47, which is controlled by SIRT6-regulated transcriptional pausing, to evade clearance by macrophages. Using osteoblast- and myeloid-specific gene knockout mice, SIRT6 is further revealed to be a critical modulator for apoOBs clearance via targeting CD47-SIRPα checkpoint. Moreover, apoOBs activate SIRT6-mediated chemotaxis to recruit macrophages by releasing apoptotic vesicles. Two targeting delivery strategies are developed to enhance SIRT6 activity, resulting in rejuvenated apoOBs clearance and delayed age-related bone loss. Collectively, the findings reveal a previously unknown linkage between immune surveillance and bone homeostasis and targeting the SIRT6-regulated mechanism can be a promising therapeutic strategy for age-related bone diseases.

Increase in Ribosomal Fidelity Benefits Salmonella upon Bile Salt Exposure.

Translational fidelity is maintained by multiple quality control steps in all three domains of life. Increased translational errors (mistranslation) occur due to genetic mutations and external stresses. Severe mistranslation is generally harmful, but moderate levels of mistranslation may be favored under certain conditions. To date, little is known about the link between translational fidelity and host–pathogen interactions. Salmonella enterica can survive in the gall bladder during systemic or chronic infections due to bile resistance. Here we show that increased translational fidelity contributes to the fitness of Salmonella upon bile salt exposure, and the improved fitness depends on an increased level of intracellular adenosine triphosphate (ATP). Our work thus reveals a previously unknown linkage between translational fidelity and bacterial fitness under bile stress.

Pectin Induced Colony Expansion of Soil-Derived Flavobacterium Strains.

The genus Flavobacterium is characterized by the capacity to metabolize complex organic compounds and a unique gliding motility mechanism. Flavobacteria are often abundant in root microbiomes of various plants, but the factors contributing to this high abundance are currently unknown. In this study, we evaluated the effect of various plant-associated poly- and mono-saccharides on colony expansion of two Flavobacterium strains. Both strains were able to spread on pectin and other polysaccharides such as microcrystalline cellulose. However, only pectin (but not pectin monomers), a component of plant cell walls, enhanced colony expansion on solid surfaces in a dose- and substrate-dependent manner. On pectin, flavobacteria exhibited bi-phasic motility, with an initial phase of rapid expansion, followed by growth within the colonized area. Proteomic and gene expression analyses revealed significant induction of carbohydrate metabolism related proteins when flavobacteria were grown on pectin, including selected SusC/D, TonB-dependent glycan transport operons. Our results show a positive correlation between colony expansion and the upregulation of proteins involved in sugar uptake, suggesting an unknown linkage between specific operons encoding for glycan uptake and metabolism and flavobacterial expansion. Furthermore, within the context of flavobacterial-plant interactions, they suggest that pectin may facilitate flavobacterial expansion on plant surfaces in addition to serving as an essential carbon source.

Reactions of 3,3′‐Linked Bispyrroles with Carbon Electrophiles

The reactivity of 3,3′‐linked bispyrroles, easily accessible by ring‐enlargement reactions of donor–acceptor cyclopropanes, towards various carbon electrophiles was investigated. A biscyclopropanated furan, equipped with imines as acceptor units, was converted by rearrangement and subsequent elimination of water to 3,3′‐linked bispyrroles. Thereby the nucleophilic 2‐position of the pyrroles stayed unsubstituted, thus permitting a further reaction with electrophiles. The heterocycles were treated with oxalyl chloride to form a new six‐membered ring between the pyrrolic subunits. The 1,2‐diketone moiety in these species was used as a starting point to extend the π‐system via a condensation reaction with aromatic 1,2‐diamines. The reaction of 3,3′‐linked bispyrroles with the phosgene surrogate triphosgene led to a seven‐membered anhydride. The use of the Vilsmeier reagent led to a formylation of the bispyrroles. Furthermore, a direct oxidative coupling between two bispyrroles resulted in a previously unknown linkage (3,3′:2′,2′′:3′′,3′′′) between four pyrrole subunits.

Familial Cortical Myoclonic Tremor and Epilepsy, an Enigmatic Disorder: From Phenotypes to Pathophysiology and Genetics. A Systematic Review.

BackgroundAutosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical reflex myoclonus. FCMTE has been described in over 100 pedigrees worldwide, under several different names and acronyms. Pathological changes have been located in the cerebellum. This systematic review discusses the clinical spectrum, treatment, pathophysiology, and genetic findings.MethodsWe carried out a PubMed search, using a combination of the following search terms: cortical tremor, myoclonus, epilepsy, benign course, adult onset, familial, and autosomal dominant; this resulted in a total of 77 studies (761 patients; 126 pedigrees) fulfilling the inclusion and exclusion criteria.ResultsPhenotypic differences across pedigrees exist, possibly related to underlying genetic differences. A “benign” phenotype has been described in several Japanese families and pedigrees linked to 8q (FCMTE1). French patients (5p linkage; FCMTE3) exhibit more severe progression, and in Japanese/Chinese pedigrees (with unknown linkage) anticipation has been suggested. Preferred treatment is with valproate (mind teratogenicity), levetiracetam, and/or clonazepam. Several genes have been identified, which differ in potential pathogenicity.DiscussionBased on the core features (above), the syndrome can be considered a distinct clinical entity. Clinical features may also include proximal myoclonus and mild progression with aging. Valproate or levetiracetam, with or without clonazepam, reduces symptoms. FCMTE is a heterogeneous disorder, and likely to include a variety of different conditions with mutations of different genes. Distinct phenotypic traits might reflect different genetic mutations. Genes involved in Purkinje cell outgrowth or those encoding for ion channels or neurotransmitters seem good candidate genes.

New statistical methods for estimation of recombination fractions in F2 population

BackgroundDominant markers in an F2 population or a hybrid population have much less linkage information in repulsion phase than in coupling phase. Linkage analysis produces two separate complementary marker linkage maps that have little use in disease association analysis and breeding. There is a need to develop efficient statistical methods and computational algorithms to construct or merge a complete linkage dominant marker maps. The key for doing so is to efficiently estimate recombination fractions between dominant markers in repulsion phases.ResultWe proposed an expectation least square (ELS) algorithm and binomial analysis of three-point gametes (BAT) for estimating gamete frequencies from F2 dominant and codominant marker data, respectively. The results obtained from simulated and real genotype datasets showed that the ELS algorithm was able to accurately estimate frequencies of gametes and outperformed the EM algorithm in estimating recombination fractions between dominant loci and recovering true linkage maps of 6 dominant loci in coupling and unknown linkage phases. Our BAT method also had smaller variances in estimation of two-point recombination fractions than the EM algorithm.ConclusionELS is a powerful method for accurate estimation of gamete frequencies in dominant three-locus system in an F2 population and BAT is a computationally efficient and fast method for estimating frequencies of three-point codominant gametes.

Hair analysis for the biomonitoring of pesticide exposure: comparison with blood and urine in a rat model

Urine and plasma have been used to date for the biomonitoring of exposure to pollutants and are still the preferred fluids for this purpose; however, these fluids mainly provide information on the short term and may present a high level of variability regarding pesticide concentrations, especially for nonpersistent compounds. Hair analysis may provide information about chronic exposure that is averaged over several months; therefore, this method has been proposed as an alternative to solely relying on these fluids. Although the possibility of detecting pesticides in hair has been demonstrated over the past few years, the unknown linkage between exposure and pesticides concentration in hair has limited the recognition of this matrix as a relevant tool for assessing human exposure. Based on a rat model in which there was controlled exposure to a mixture of pesticides composed of lindane, β-hexachlorocyclohexane, β-endosulfan, p,p′-DDT, p,p′-DDE, dieldrin, pentachlorophenol, diazinon, chlorpyrifos, cyhalothrin, permethrin, cypermethrin, propiconazole, fipronil, oxadiazon, diflufenican, trifluralin, carbofuran, and propoxur, the current work demonstrates the association between exposure intensity and resulting pesticide concentration in hair. We also compared the results obtained from a hair analysis to urine and plasma collected from the same rats. Hair, blood, and urine were collected from rats submitted to 90-day exposure by gavage to the aforementioned mixture of common pesticides at different levels. We observed a linear relationship between exposure intensity and the concentration of pesticides in the rats’ hair (RPearson 0.453–0.978, p < 0.01). A comparison with results from urine and plasma samples demonstrated the relevance of hair analysis and, for many chemicals, its superiority over using fluids for differentiating animals from different groups and for re-attributing animals to their correct groups of exposure based on pesticide concentrations in the matrix. Therefore, this study strongly supports hair analysis as a reliable tool to be used during epidemiological studies to investigate exposure-associated adverse health effects.

DELAY OF GERMINATION1 (DOG1) regulates both seed dormancy and flowering time through microRNA pathways

Seed germination and flowering, two critical developmental transitions in plant life cycles, are coordinately regulated by genetic and environmental factors to match plant establishment and reproduction to seasonal cues. The DELAY OF GERMINATION1 (DOG1) gene is involved in regulating seed dormancy in response to temperature and has also been associated genetically with pleiotropic flowering phenotypes across diverse Arabidopsis thaliana accessions and locations. Here we show that DOG1 can regulate seed dormancy and flowering times in lettuce (Lactuca sativa, Ls) and Arabidopsis through an influence on levels of microRNAs (miRNAs) miR156 and miR172. In lettuce, suppression of LsDOG1 expression enabled seed germination at high temperature and promoted early flowering in association with reduced miR156 and increased miR172 levels. In Arabidopsis, higher miR156 levels resulting from overexpression of the MIR156 gene enhanced seed dormancy and delayed flowering. These phenotypic effects, as well as conversion of MIR156 transcripts to miR156, were compromised in DOG1 loss-of-function mutant plants, especially in seeds. Overexpression of MIR172 reduced seed dormancy and promoted early flowering in Arabidopsis, and the effect on flowering required functional DOG1 Transcript levels of several genes associated with miRNA processing were consistently lower in dry seeds of Arabidopsis and lettuce when DOG1 was mutated or its expression was reduced; in contrast, transcript levels of these genes were elevated in a DOG1 gain-of-function mutant. Our results reveal a previously unknown linkage between two critical developmental phase transitions in the plant life cycle through a DOG1-miR156-miR172 interaction.

Polyamine Metabolism Is Sensitive to Glycolysis Inhibition in Human Neuroblastoma Cells

Polyamines are essential for cell proliferation, and their levels are elevated in many human tumors. The oncogene n-myc is known to potentiate polyamine metabolism. Neuroblastoma, the most frequent extracranial solid tumor in children, harbors the amplification of n-myc oncogene in 25% of the cases, and it is associated with treatment failure and poor prognosis. We evaluated several metabolic features of the human neuroblastoma cell lines Kelly, IMR-32, and SK-N-SH. We further investigated the effects of glycolysis impairment in polyamine metabolism in these cell lines. A previously unknown linkage between glycolysis impairment and polyamine reduction is unveiled. We show that glycolysis inhibition is able to trigger signaling events leading to the reduction of N-Myc protein levels and a subsequent decrease of both ornithine decarboxylase expression and polyamine levels, accompanied by cell cycle blockade preceding cell death. New anti-tumor strategies could take advantage of the direct relationship between glucose deprivation and polyamine metabolism impairment, leading to cell death, and its apparent dependence on n-myc. Combined therapies targeting glucose metabolism and polyamine synthesis could be effective in the treatment of n-myc-expressing tumors.

Enterobacterial common antigen and O-specific polysaccharide coexist in the lipopolysaccharide of Yersinia enterocolitica serotype O : 3

Yersinia enterocolitica serotype O : 3 produces two types of lipopolysaccharide (LPS) molecules to its surface. In both types the lipid A (LA) structure is substituted by inner core (IC) octasaccharide to which either outer core (OC) hexasaccharide or homopolymeric O-polysaccharide (OPS) is linked. In addition, enterobacterial common antigen (ECA) can be covalently linked to LPS, however, via an unknown linkage. To elucidate the relationship between ECA and LPS in Y. enterocolitica O : 3 and the effect of temperature on their expression, LPS was isolated from bacteria grown at 22 °C and 37 °C by consequent hot phenol/water and phenol-chloroform-light petroleum extractions to obtain LPS preparations free of ECA linked to glycerophospholipid. In immunoblotting, monoclonal antibodies TomA6 and 898, specific for OPS and ECA, respectively, reacted both with ladder-like bands and with a slower-migrating smear suggesting that the ECA and OPS epitopes coexist on the same molecules. These results were supported by immunoblotting with a monovalent Y. enterocolitica O : 3 ECA-specific rabbit antiserum. Also, two or three 898-positive (and monovalent-positive) TomA6-negative bands migrated at the level of the LA-IC band in LPS samples from certain OC mutants, most likely representing LA-IC molecules carrying 1-3 ECA repeat units but no OPS. These bands were also present in Y. enterocolitica O : 9 OC mutants; however, coexistence of ECA and OPS in the same molecules could not be detected. Finally, the LA-IC-ECA bands were missing from LPS of bacteria grown at 37 °C and also the general reduction in wild-type bacteria of ECA-specific monovalent-reactive material at 37 °C suggested that temperature regulates the expression of ECA. Indeed, RNA-sequencing analysis showed significant downregulation of the ECA biosynthetic gene cluster at 37 °C.

Molecular characterisation of resistance against potato wart races 1, 2, 6 and 18 in a tetraploid population of potato (Solanum tuberosum subsp. tuberosum)

Potato wart is caused by the obligate biotrophic fungus Synchytrium endobioticum, which is subject to quarantine regulations due to the production of long persisting spores in the soil and the lack of effective fungicides. The objective of this study was to identify quantitative trait loci (QTL) for resistance against potato wart races (R) 1, 2, 6 and 18 in a tetraploid potato population developed by crossing cv. Saturna (resistant to R1) with cv. Panda (resistant to R1, R2, R6, R18). A total of 92 progenies were used for phenotyping and genotyping. Resistance tests were performed for races 1 and 18 in 2 years and for races 2 and 6 in 1 year on 10 to 20 eyepieces per genotype. Based on amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers, linkage maps were established for the female and male parent, respectively. Single marker analysis followed by a multiple regression analysis revealed initial marker-trait associations. The interval mapping routine of TetraploidMap was applied for QTL analysis. A major QTL for resistance against race 1 explaining between 46 % and 56 % of the phenotypic variation was identified near Sen1, a known resistance locus for potato wart race 1 on chromosome XI. Other resistance QTL were detected on chromosomes I (to R2), II (to R6, 18), VI (to R1, 2, 6, 18), VII (to R2, 6, 18), VIII (to R1, 2, 6, 18), X (to R2, 6, 18), XI (to R2, 6, 18) and on an unknown linkage group (to R18) explaining minor to moderate effects of the phenotypic variation. Resistance QTL against different potato wart races often overlapped, particularly concerning races 2, 6 and 18. Overall, this study gives a valuable insight into the complex inheritance of resistance against potato wart.

Tubulin tyrosination navigates the kinesin-1 motor domain to axons

Neurons form distinctive axonal and dendritic compartments that are important for directional signaling, but the mechanisms that discriminate between axons and dendrites remain elusive. Previous studies have demonstrated that the kinesin-1 motor domain is capable of distinguishing the axon from dendrites. Here we found that the amino acid substitutions in the beta5-loop8 region transformed truncated kinesin-1 from a uni-destination (that is, the axon-specific destination) to a bi-destination (that is, axons and dendrites) state. Furthermore, tyrosinated tubulins that are abundant in somatodendrites prevent the wild-type kinesin-1 from binding to microtubules, whereas the bi-destination-type kinesin-1 does not have this inhibition. Consistently, inhibition of tubulin tyrosination in rat hippocampal neurons resulted in the distribution of truncated kinesin-1 in both axons and dendrites. Our study identifies a molecular mechanism that discriminates the axonal microtubules from somatodendritic microtubules, as well as a previously unknown linkage between tubulin modification and polarized trafficking in neurons.

A Cdo–Bnip-2–Cdc42 signaling pathway regulates p38α/β MAPK activity and myogenic differentiation

The p38α/β mitogen-activated protein kinase (MAPK) pathway promotes skeletal myogenesis, but the mechanisms by which it is activated during this process are unclear. During myoblast differentiation, the promyogenic cell surface receptor Cdo binds to the p38α/β pathway scaffold protein JLP and, via JLP, p38α/β itself. We report that Cdo also interacts with Bnip-2, a protein that binds the small guanosine triphosphatase (GTPase) Cdc42 and a negative regulator of Cdc42, Cdc42 GTPase-activating protein (GAP). Moreover, Bnip-2 and JLP are brought together through mutual interaction with Cdo. Gain- and loss-of-function experiments with myoblasts indicate that the Cdo–Bnip-2 interaction stimulates Cdc42 activity, which in turn promotes p38α/β activity and cell differentiation. These results reveal a previously unknown linkage between a cell surface receptor and downstream modulation of Cdc42 activity. Furthermore, interaction with multiple scaffold-type proteins is a distinctive mode of cell surface receptor signaling and provides one mechanism for specificity of p38α/β activation during cell differentiation.

A New Strategy for Estimating Recombination Fractions Between Dominant Markers From an F2 Population

Although most high-density linkage maps have been constructed from codominant markers such as single-nucleotide polymorphisms (SNPs) and microsatellites due to their high linkage information, dominant markers can be expected to be even more significant as proteomic technique becomes widely applicable to generate protein polymorphism data from large samples. However, for dominant markers, two possible linkage phases between a pair of markers complicate the estimation of recombination fractions between markers and consequently the construction of linkage maps. The low linkage information of the repulsion phase and high linkage information of coupling phase have led geneticists to construct two separate but related linkage maps. To circumvent this problem, we proposed a new method for estimating the recombination fraction between markers, which greatly improves the accuracy of estimation through distinction between the coupling phase and the repulsion phase of the linked loci. The results obtained from both real and simulated F2 dominant marker data indicate that the recombination fractions estimated by the new method contain a large amount of linkage information for constructing a complete linkage map. In addition, the new method is also applicable to data with mixed types of markers (dominant and codominant) with unknown linkage phase.

Sibship T2 association tests of complex diseases for tightly linked markers

For population case-control association studies, the false-positive rates can be high due to inappropriate controls, which can occur if there is population admixture or stratification. Moreover, it is not always clear how to choose appropriate controls. Alternatively, the parents or normal sibs can be used as controls of affected sibs. For late-onset complex diseases, parental data are not usually available. One way to study late-onset disorders is to perform sib-pair or sibship analyses. This paper proposes sibship-based Hotelling's T2 test statistics for high-resolution linkage disequilibrium mapping of complex diseases. For a sample of sibships, suppose that each sibship consists of at least one affected sib and at least one normal sib. Assume that genotype data of multiple tightly linked markers/haplotypes are available for each individual in the sample. Paired Hotelling's T2 test statistics are proposed for high-resolution association studies using normal sibs as controls for affected sibs, based on two coding methods: 'haplotype/allele coding' and 'genotype coding'. The paired Hotelling's T2 tests take into account not only the correlation among the markers, but also take the correlation within each sib-pair. The validity of the proposed method is justified by rigorous mathematical and statistical proofs under the large sample theory. The non-centrality parameter approximations of the test statistics are calculated for power and sample size calculations. By carrying out power and simulation studies, it was found that the non-centrality parameter approximations of the test statistics were accurate. By power and type I error analysis, the test statistics based on the 'haplotype/allele coding' method were found to be advantageous in comparison to the test statistics based on the 'genotype coding' method. The test statistics based on multiple markers can have higher power than those based on a single marker. The test statistics can be applied not only for bi-allelic markers, but also for multi-allelic markers. In addition, the test statistics can be applied to analyse the genetic data of multiple markers which contain double heterozygotes -- that is, unknown linkage phase data. An SAS macro, Hotel_sibs.sas, is written to implement the method for data analysis.

Outcomes associated with hypogonadism in women with chronic kidney disease

Outcomes associated with hypogonadism in women with chronic kidney disease

The effect of using approximate gametic variance covariance matrices on marker assisted selection by BLUP.

Under additive inheritance, the Henderson mixed model equations (HMME) provide an efficient approach to obtaining genetic evaluations by marker assisted best linear unbiased prediction (MABLUP) given pedigree relationships, trait and marker data. For large pedigrees with many missing markers, however, it is not feasible to calculate the exact gametic variance covariance matrix required to construct HMME. The objective of this study was to investigate the consequences of using approximate gametic variance covariance matrices on response to selection by MABLUP. Two methods were used to generate approximate variance covariance matrices. The first method (Method A) completely discards the marker information for individuals with an unknown linkage phase between two flanking markers. The second method (Method B) makes use of the marker information at only the most polymorphic marker locus for individuals with an unknown linkage phase. Data sets were simulated with and without missing marker data for flanking markers with 2, 4, 6, 8 or 12 alleles. Several missing marker data patterns were considered. The genetic variability explained by marked quantitative trait loci (MQTL) was modeled with one or two MQTL of equal effect. Response to selection by MABLUP using Method A or Method B were compared with that obtained by MABLUP using the exact genetic variance covariance matrix, which was estimated using 15 000 samples from the conditional distribution of genotypic values given the observed marker data. For the simulated conditions, the superiority of MABLUP over BLUP based only on pedigree relationships and trait data varied between 0.1% and 13.5% for Method A, between 1.7% and 23.8% for Method B, and between 7.6% and 28.9% for the exact method. The relative performance of the methods under investigation was not affected by the number of MQTL in the model.