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Genetic variation in memory functioning.

On the basis of a review of the literature the contribution of genetic factors for individual differences in memory performance is discussed. Explorations of such influences on memory have just begun. Most of those studies that have been conducted in order to find a quantitative trait locus for memory have focused on ApolipoproteinE (ApoE). One form of this gene is strongly associated with cardiovascular disease in middle age and to late-onset Alzheimer's disease. Some studies have demonstrated an association between ApoE and memory even in non-demented individuals. Other studies have failed to demonstrate this association. Based on data from a prospective cohort study (Betula) in our own laboratory, we have assessed and examined associations between three different forms of ApoE and performance on episodic memory tests. Cross-sectional comparisons revealed non-significant differences in episodic memory performance between carriers of the three alleles. Analyses of change scores in longitudinal data revealed that allele epsilon 4 was related to a lower level of memory performance than alleles epsilon 2 and epsilon 3. This effect was most pronounced in tasks providing cognitive support at both encoding and retrieval, suggesting a deficit in utilizing such support in carriers of the epsilon 4 allele.

Aging↗

Individual and multi-environment combined analyses identify QTLs for morphogenetic and reproductive development traits in white clover (Trifolium repens L.).

White clover (Trifolium repens L.) is a key component legume of temperate pasture agriculture and an important target for molecular marker-assisted plant breeding. A genetic map of white clover has been used to assess genetic control of agronomically important traits that vary in the F2(I.4RxI.5J) mapping family. Phenotypic analysis was performed for a range of vegetative morphogenesis traits (such as leaf area, internode length, plant height and plant spread) and reproductive morphogenesis and development traits (such as flowering date, floral intensity and seed yield), with both spatial and temporal replication. A multi-environment combined analysis (combined analysis) has been performed for traits assessed across multiple experimental datasets in order to identify consistent genetic effects. Quantitative trait locus (QTLs) were detected for the majority of traits, and the locations and magnitudes of QTL effects were compared between individual and combined analyses. This molecular genetic dissection of agronomic traits in white clover provides the basis for equivalent studies in more complex populations, design of marker-assisted selection strategies and comparative genetics with model legume species. Selection for QTLs derived from the combined analysis will permit robust improvement of phenotypic traits over different environments.

Chromosome Mapping↗

Two tightly linked QTLs modify tomato sugar content via different physiological pathways.

Congenic lines that differ in a single defined chromosome segment are useful for the study of complex phenotypes, as they allow isolation of the effect of a particular quantitative trait locus (QTL) from those of the entire genome. We conducted high-resolution QTL mapping of a 9-cM introgression, originating from the wild tomato species Lycopersicon pennellii, in two extremely different genetic and physiological backgrounds. In the "indeterminate" glasshouse background we identified only a single QTL ( Brix9-2-5) that affects the total soluble solids of the fruit [mainly sugars, measured in Brix units (B)]. This QTL was previously delimited within the gene for an apoplastic invertase, Lin5, that modulates sugar partitioning to the fruit. Analysis of the effects of the same chromosome segment in "determinate", open-field tomatoes, revealed two QTLs, 0.3 cM apart: the fruit-specific Brix9-2-5 that affects B only, and the shoot-specific PW9-2-5, which accounts for an altered growth habit resulting in increases in plant weight, yield, and B. This study highlights the power of the congenic approach for dissecting developmental pathways leading to complex phenotypes.

Base Sequence↗

Interaction between the X chromosome and an autosome regulates size sexual dimorphism in Portuguese Water Dogs.

Size sexual dimorphism occurs in almost all mammals. In Portuguese Water Dogs, much of the difference in skeletal size between females and males is due to the interaction between a Quantitative Trait Locus (QTL) on the X-chromosome and a QTL linked to Insulin-like Growth Factor 1 (IGF-1) on the CFA 15 autosome. In females, the haplotype of CFA 15 resulting in small size is dominant. In males, the haplotype for large size is dominant. Females, homozygous at the CHM marker on the X chromosome and homozygous for the large size CFA 15 haplotype are, on average, as large as large males. However, all females that are heterozygous at the CHM marker are small, regardless of their CFA 15 genotype. This interaction suggests a genetic mechanism that in turn leads to a scenario for the evolution of size sexual dimorphism consistent with a proposal of Lande that sexual dimorphism can evolve because females secondarily become smaller than males as a consequence of natural selection for optimal size. Our results also can explain Rensch's Rule, which states that size is often positively correlated with the level of size sexual dimorphism.

Animals↗

Mapping of QTLs prolonging the latent period of Puccinia triticina infection in wheat.

Slow rusting is considered a crucial component of durable resistance to wheat leaf rust caused by Puccinia triticina and is often expressed in the form of a prolonged latent period. Selection for a longer latent period is considered an effective approach to developing wheat cultivars with improved durable resistance to leaf rust. A recombinant inbred line (RIL) population derived from CI 13227 (long latent period) x Suwon 92 (short latent period) was phenotyped for latent period in two greenhouse experiments in separate years, and amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers were analyzed in the same population. Among the RILs, the frequency distribution for latent period was continuous, and latent period was highly correlated between years (r=0.94, P<0.0001). A quantitative trait locus (QTL) prolonging the latent period of P. triticina, designated as QLrlp.osu-2DS, explained 42.8% and 54.5% of the phenotypic and genetic variance in the two experiments, respectively. QLrlp.osu-2DS was mapped on the distal region of chromosome 2DS. Two other QTLs for latent period, QLrlp.osu-2B and QLrlp.osu-7BL, were localized on chromosome 2B and the long arm of chromosome 7B, respectively. Multiple regression analysis showed that these three QTLs collectively explained 58.0% and 73.8% of the phenotypic and genetic variance over two experiments, respectively. Fourteen RILs that carried all three alleles for long latent period at three AFLP loci flanking QLrlp.osu-2DS, QLrlp.osu-2B, and QLrlp.osu-7BL had a mean latent period of 12.5 days, whereas 13 RILs without any long-latent-period alleles at the corresponding loci had a mean latent period of 7.4 days. Three SSR markers closely linked to these QTLs have potential to be applied in marker-assisted selection for prolonged latent period in wheat.

Basidiomycota↗

Genetic regulation of endotoxin-induced airway disease.

To identify novel genes regulating the biologic response to lipopolysaccharide (LPS), we used a combination of quantitative trait locus (QTL) analysis and microarray-based gene expression studies of C57BL/6J x DBA/2J(BXD) F2 and recombinant inbred (RI) mice. A QTL affecting pulmonary TNF-alpha production was identified on chromosome 2, and a region affecting both polymorphonuclear leukocyte recruitment and TNF-alpha levels was identified on chromosome 11. Microarray analyses of unchallenged and LPS-challenged BXD RI strains identified approximately 500 genes whose expression was significantly changed by inhalation of LPS. Of these genes, 28 reside within the chromosomal regions identified by the QTL analyses, implicating these genes as high priority candidates for functional studies. Additional high priority candidate genes were identified based on their differential expression in mice having high and low responses to LPS. Functional studies of these genes are expected to reveal important molecular mechanisms regulating the magnitude of biologic responses to LPS.

Animals↗

Mapping quantitative trait loci that influence femoral cross-sectional area in mice.

Size and shape are critical determinants of the mechanical properties of skeletal elements and can be anticipated to be highly heritable. Moreover, the genes responsible may be independent of those that regulate bone mineral density (BMD). To begin to identify the heritable determinants of skeletal geometry, we have examined femoral cross-sectional area (FCSA) in male and female mice from two inbred strains of mice with divergent FCSA (C57BL/6 [B6] and DBA/2 [D2]), a large genetically heterogeneous population (n = 964) of B6D2F2 mice and 18 BXD recombinant inbred (RI) strains derived from their F2 cross. Femora were harvested from 16-week-old mice and FCSA (bone and marrow space enclosed within the periosteum) was measured at the midshaft by digital image analysis. In all mouse populations examined, FCSA was positively correlated with body weight and weight-corrected FCSA (WC-FCSA) values were normally distributed in the BXD-RI and F2 populations, suggesting polygenic control of this trait. Genome-wide quantitative trait locus (QTL) analysis of the B6D2F2 population revealed regions on four different chromosomes that were very strongly linked to WC-FCSA (chromosomes 6, 8, 10, and X) in both genders. Evidence of gender-specific genetic influences on femoral geometry was also identified at three other chromosomal sites (chromosomes 2, 7, and 12). Supporting evidence for the WC-FCSA QTLs on chromosomes 2, 7, 8, 10, and 12 also was present in the RI strains. Interestingly, none of these WC-FCSA QTLs were identified in our previous QTL analysis of whole body BMD in the same B6D2F2 population. Thus, the genetic determinants of bone size appear to be largely, if not entirely, distinct from those that regulate BMD attainment. The identification of the genes responsible for geometric differences in bone development should reveal fundamentally important processes in the control of skeletal integrity.

Animals↗

Genetics of dietary obesity in AKR/J x SWR/J mice: segregation of the trait and identification of a linked locus on chromosome 4.

We describe a new multiple gene mouse model of differential sensitivity to dietary obesity that provides a tool for dissecting the genetic basis for body composition and obesity. AKR/J and SWR/J male mice, as well as male progeny of intercrosses between these strains, were fed a high-fat diet for 12 weeks beginning at 5 weeks of age. Body weight and energy intake were assessed weekly. At the conclusion of the dietary manipulation, an adiposity index was calculated by dividing the weight of seven dissected adipose depots by the carcass weight. AKR/J mice had approximately sixfold greater adiposity than SWR/J mice. Examination of the segregation of the adiposity trait in the progeny of crosses between these strains indicates that the trait is determined by a minimum of one to four genetic loci and that there is significant dominance of the AKR/J genotype. A preliminary analysis with markers linked to the known mouse obesity genes ob, db, tub, and fat showed no linkage with these loci. However, a quantitative trait locus was found that maps distal to the db gene on Chromosome (Chr) 4. This locus has been designated dietary obese 1 or Do1.

Alleles↗

Genetics of adaptive radiation in Hawaiian species of Tetramolopium (Asteraceae). III. Evolutionary genetics of sex expression.

Despite numerous studies of speciation on oceanic islands, few insights exist on the genetic changes involved in the origin and diversification of island taxa. Here we report a genetic analysis of the evolutionary change in sex expression in Hawaiian Tetramolopium. The most diverse clade in the genus is characterized by a monoecious breeding system. The breeding system resulted from a change in sex expression in disc florets from the ancestral hermaphroditic condition to the derived male state. Analysis of an F2 population from a cross between the two forms of sex expression indicates two regions of the Tetramolopium linkage map are associated with the loss of female function in disc florets. Quantitative trait locus mapping of the two linkage groups confirms that two loci control 56% of the phenotypic variation of the trait in the F2 population. Additive and dominance effects are apparent but no statistical evidence of epistasis was found. Several related reproductive traits also have few genetic associations on the linkage map, but are generally distinct from the control of sex expression. Although modifier loci are likely to be involved, the apparent simple genetic change underlying sex expression parallels a major evolutionary diversification in Hawaiian Tetramolopium and may have initiated the divergence of this novel clade.

Adaptation, Biological↗

Identification of a mutation in ADD1/SREBP-1 in the spontaneously hypertensive rat.

It has recently been proposed that primary mutations in genes involved in fatty acid and lipid metabolism may contribute to the pathogenesis of insulin resistance and dyslipidemia often observed in spontaneous forms of hypertension. In the current study in the spontaneously hypertensive rat (SHR), we mapped and sequenced the gene encoding a key transcription factor known as ADD1 (adipocyte determination and differentiation factor 1) or SREBP-1c (sterol regulatory element binding protein- c) that has recently been identified as a master regulator of genes involved in the hepatic control of lipid and carbohydrate metabolism. We found that (1) the gene for ADD1/SREBP-1c maps to a region of rat Chromosome 10 previously reported to contain a quantitative trait locus involved in the regulation of hepatic cholesterol levels and (2) the SHR harbors a valine-to-methionine substitution in the COOH terminal portion of the ADD1/SREBP-1 protein that is not present in 44 other strains of laboratory rats. These findings, together with previous studies showing that transgenic expression of SREBP-1 isoforms has major effects on hepatic fatty acid and cholesterol biosynthesis, suggest that naturally occurring variation in the gene encoding the SREBP-1 isoforms might contribute to inherited variation in lipid metabolism in the SHR versus other strains of rats. These results should serve to motivate future transfection studies of the effect of the SHR mutant on SREBP-1 expression and activation in vitro, as well as the development of congenic and transgenic strains of SHR to investigate the effects of different variants of SREBP-1 on carbohydrate and lipid metabolism in vivo.

Amino Acid Sequence↗

An entropy-based measure of founder informativeness.

Optimizing quantitative trait locus (QTL) mapping experiments requires a generalized measure of marker informativeness because variable information is obtained from different marker systems, marker distribution and pedigree types. Such a measure can be derived from the concept of Shannon entropy, a central concept in information theory. Here we introduce entropy-based founder informativeness (EFI), a new measure of information content generalized across pedigrees, maps, marker systems and mating configurations. We derived equations for inbred- and outbred-derived mapping populations. Mathematical properties of EFI include enhanced sensitivity to mapping population type and extension to any number of founders. To illustrate the use of EFI, we compared experimental designs for QTL mapping for three examples: (i) different marker systems for an F2 pedigree, (ii) different marker densities and sampling sizes for a BC1 pedigree and (iii) a comparison of haplotypic versus zygotic analyses of an outbred pedigree. As an a priori generalized measure of information content, EFI does not require phenotypic data for optimizing experimental designs for QTL mapping.

Alleles↗

Gender specificity in the genetic determinants of peak bone mass.

Peak bone mass is a major determinant of osteoporotic fracture risk. Gender differences in peak bone mass acquisition are well recognized in humans and may account for a substantial share of the increased prevalence of fragility fractures in women compared with men. Skeletal development is regulated by both heritable and environmental factors. Experimental animal models provide a means to circumvent complicating environmental factors. In this study we examined the heritability of peak bone mineral density (BMD) in genetically distinct laboratory mouse strains raised under strict environmental control and sought to identify genetic loci that may contribute to gender differences in this skeletal phenotype. Peak whole body BMD of male and female mice from a panel of 18 recombinant inbred (RI) strains derived from a cross between C57BL/6 and DBA/2 progenitors (BXD) was measured by dual-energy X-ray absorptiometry (DXA). A highly significant relationship existed between body weight and BMD in the BXD RI mice (r2 = 0.25; p = 1 x 10(-43)). To allow for comparison between male and female RI strains, whole body BMD values were corrected for the influence of body weight. The distribution of weight-corrected BMD (WC-BMD) values among the strains indicated the presence of strong genetic influences in both genders, with an estimated narrow sense heritability of 45% and 22% in male and female mice, respectively. Comparison of RI strain results by two-way analysis of variance (ANOVA) revealed a significant strain-by-gender interaction (F1,17,479 = 6.13; p < 0.0001). Quantitative trait locus (QTL) analysis of the BXD RI strain series provisionally identified nine chromosomal sites linked to peak bone mass development in males and seven regions in females. In two cases, the provisional chromosomal loci were shared between genders, but in most cases they were distinct (five female-specific QTLs and six male-specific QTLs). QTL analysis of a genetically heterogeneous F2 population derived from the B6 and D2 progenitor strains provided additional support for the gender specificity of two loci. A significant phenotype-genotype correlation was only observed in male F2 mice at microsatellite marker D7Mit114 on chromosome 7, and a correlation at D2Mit94 on chromosome 2 was only observed in female F2 mice. The present data highlight the important role of gender in the genetic basis of peak bone mass in laboratory mice. Because the male phenotype is associated with considerable fracture risk reduction, an elucidation of the nature of that effect could provide the basis for novel diagnostic, preventative, or therapeutic approaches.

Animals↗

Holistic approaches for improvement of maize resistance against lodging stress: current status and future perspective.

Lodging is a major constraint in maize production, causing significant yield losses, reduced grain quality, and harvesting inefficiencies, thereby posing a serious challenge to global food security and climate-resilient agriculture. This review synthesizes current knowledge on the genetic, physiological, and agronomic determinants of maize lodging resistance and evaluates holistic strategies for improving tolerance to lodging stress. Recent advances in quantitative trait locus (QTL) mapping, genome-wide association studies (GWAS), functional gene characterization, genome editing, high-throughput phenotyping, and precision agronomy have provided powerful tools to enhance stalk biomechanics, root anchorage, and adaptive plant architecture. Integrating genomic discovery with advanced phenomics and optimized agronomic management offers a scalable framework for accelerating the development of high-yielding, lodging-resilient maize cultivars. However, critical gaps remain in understanding the genetic coordination between stalk strength and root system architecture, integrating multi-omics approaches to unravel regulatory networks, validating genome-editing interventions across diverse agro-ecologies, and developing environment-responsive predictive breeding models and cost-effective phenotyping tools, particularly for stress-prone regions. Addressing these challenges through coordinated multi-environment trials and integrative molecular-agronomic strategies will facilitate the translation of genomic discoveries into climate-resilient, high-performing maize cultivars. By consolidating molecular insights with applied breeding and management practices, this review provides a comprehensive framework that guides researchers in designing genome-informed and field-validated approaches to improve maize resistance to lodging stress and support sustainable crop production systems.

Zea mays↗

Vacuolar invertase regulates elongation of Arabidopsis thaliana roots as revealed by QTL and mutant analysis.

The possible role of the sucrose-splitting enzymes sucrose synthase and invertase in elongating roots and hypocotyls of Arabidopsis was tested by using a combination of histochemical methods and quantitative trait locus (QTL) analysis. Lengths of roots and hypocotyls correlated better with invertase activities than with sucrose synthase activities. The highest correlations were observed with activities in the elongating zones of roots. The genetic basis of these correlations was studied by using QTL analysis. Several loci, affecting invertase activity, colocated with loci that had an effect on root or hypocotyl length. Further fine mapping of a major locus for root length, but not for hypocotyl length (top chromosome 1), consistently showed colocation with the locus for invertase activity containing a gene coding for a vacuolar invertase. The analysis of a functional knockout line confirmed the role of this invertase in root elongation, whereas other invertase genes might play a role in hypocotyl elongation. Thus, we show the power of QTL analysis, combined for morphological and biochemical traits, followed by fine-mapping and mutant analysis, in unraveling the function of genes and their role in growth and development.

Arabidopsis↗

A unified framework for mapping quantitative trait loci in bivalent tetraploids using single-dose restriction fragments: a case study from alfalfa.

The development of statistical methodologies for quantitative trait locus (QTL) mapping in polyploids is complicated by complex polysomic inheritance. In this article, we propose a statistical method for mapping QTL in tetraploids undergoing bivalent formation at meiosis by using single-dose restriction fragments. Our method is based on a unified framework, one that uses chromosome bivalent pairing configuration and gametic recombination to discern different mechanisms of gamete formation. Our bivalent polyploid model can not only provide a simultaneous estimation of the linkage and chromosome pairing configuration-a cytological parameter of evolutionary and systematic interest-but also enhances the precision of estimating QTL effects and position by correctly characterizing gene segregation during polyploid meiosis. By using our method and a linkage map constructed in a previous study, we successfully identify several QTL affecting winter hardiness in bivalent tetraploid alfalfa. Moreover, our results reveal significant preferential chromosome pairing at meiosis in an F1 hybrid population, which indicates the importance of reassessing the traditional view of random chromosome segregation in alfalfa.

Chromosome Pairing↗

Association of a lithogenic Abcg5/Abcg8 allele on Chromosome 17 (Lith9) with cholesterol gallstone formation in PERA/EiJ mice.

To examine further the genetic determinants of cholesterol gallstone susceptibility in inbred mice, we performed quantitative trait locus (QTL) analysis of an intercross of gallstone-susceptible PERA/EiJ and gallstone-resistant DBA/2J inbred mice. Three hundred twenty-four F2 offspring were phenotyped for cholelithiasis during consumption of a lithogenic diet and genotyped using microsatellite markers. Linkage analysis was performed by interval mapping. In addition, we analyzed the combined datasets from this cross and from an independent cross of strain PERA and gallstone-resistant I/Ln mice. QTL mapping detected one significant new gallstone susceptibility (Lith) locus on Chromosome 13 (Lith15). A second significant QTL on Chr 6 (Lith16) confirmed a previous QTL. Furthermore, suggestive QTLs confirmed Lith loci from previous crosses on Chromosomes 1, 2, 5, 16 and X. QTL analysis of the dataset derived from the combined crosses increased the detection power and narrowed confidence intervals of Lith loci on Chromosomes 2, 6, 13, and 16. Moreover, the analysis of combined datasets revealed a shared QTL between both crosses on Chromosome 17 (Lith9). Significantly higher mRNA expression of Abcg5 and Abcg8 in strain PERA compared with strains I/Ln and DBA/2 further substantiated that the PERA allele of Abcg5/Abcg8 was responsible for lithogenicity underlying Lith9.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

Identification of QTLs associated with Fusarium head blight resistance in Zhedar 2 barley.

Fusarium head blight (FHB) in barley and wheat, caused by Fusarium graminearum, is a continual problem worldwide. Primarily, FHB reduces yield and quality, and results in the production of the toxin deoxynivalenol (DON), which can affect food safety. Identification of QTLs for FHB severity, DON level and related traits heading-date (HD) and plant-height (HT) with consistent effects across a set of environments, would provide the basis for marker-assisted selection (MAS) and potentially increase the efficiency of selection for resistance. A segregating population of 75 double-haploid lines, developed from the three-way cross Zhedar 2/ND9712//Foster, was used for genome mapping and FHB severity evaluation. A linkage map of 214 RFLP, SSR and AFLP markers was constructed. Phenotypic data were collected in replicated field trials from five environments in two growing seasons. The data were analyzed using MQTL software to detect quantitative trait locus (QTL) x environment (E) interactions. Because of the presence of QTL x E, the MQM procedure in MAPQTL was applied to identify QTLs in single environments. We identified nine QTLs for FHB severity and five for low DON. Many of the disease-related QTLs identified were coincident with FHB QTLs identified in previous studies. Only two of the QTLs identified in this study were consistent across all five environments, and both were Zhedar 2 specific. Five of the FHB QTLs were associated with HD, and two were associated with HT. Regions that appear to be promising candidates for MAS and further genetic analysis include the two FHB QTLs on chromosome 2H and one on 6H, which were also associated with low DON and later heading-date in multiple environments. This study provides a starting point for manipulating Zhedar 2-derived resistance by MAS in barley to develop cultivars that will show effective resistance under disease pressure.

Chromosome Mapping↗

Utilization of marker-assisted congenics to map two blood pressure quantitative trait loci in Dahl rats.

A broad Chromosome (Chr) 10 region of the Dahl salt-sensitive (S) rat was shown by linkage and the use of congenic strains to contain a blood pressure (BP) quantitative trait locus (QTL). To further narrow down the region harboring the QTL, four congenic strains carrying smaller segments were made by replacing various segments of the S rats with the homologous segments of the Lewis (LEW) rats. The construction of these congenic strains was facilitated by a genome-wide marker screening. One congenic strain, assigned as S.L4, showed a BP-lowering effect, and the region harboring a BP QTL, designated QTL1, is localized to a segment of about 15 cM. Two other strains, assigned as S.L2 and S.L5, contained an overlapping segment, and both showed a BP-lowering effect. In contrast, the fourth congenic strain, assigned as S.L1, contained a smaller and shared fragment with S.L2 and S.L5, but it did not have a BP-lowering effect. Deducing from the segment in common in S.L2 and S.L5, and not shared between S.L1 and both congenic strains S.L2 and S.L5, the region harboring a QTL, designated as QTL2, was narrowed to about 12 cM. The current work showed the general applicability of the 'speed congenic' approach to map and fine-map BP QTL.

Animals↗