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A QTL affecting daily feed intake maps to Chromosome 2 in pigs.

Our understanding of the molecular genetic basis of several key performance traits in pigs has been significantly advanced through the quantitative trait loci (QTL) mapping approach. However, in contrast to growth and fatness traits, the genetic basis of feed intake traits has rarely been investigated through QTL mapping. Since feed intake is an important component of efficient pig production, the identification of QTL affecting feed intake may lead to the identification of genetic markers that can be used in selection programs. In this study a QTL analysis for feed intake, feeding behavior, and growth traits was performed in an F2 population derived from a cross between Chinese Meishan and European Large White pigs. A QTL with a significant effect on daily feed intake (DFI) was identified on Sus scrofa Chromosome 2 (SSC2). A number of suggestive QTL with effects on daily gain, feed conversion, and feeding behavior traits were also located. The significant QTL lies close to a previously identified mutation in the insulin-like growth factor 2 gene (IGF2) that affects carcass composition traits, although the IGF2 mutation is not segregating in the populations analyzed in the current study. Therefore, a distinct causal variant may exist on the P arm of SSC2 with an effect on feed intake.

Animals↗

Genetic analysis of seed-soluble oligosaccharides in relation to seed storability of Arabidopsis.

Seed oligosaccharides (OSs) and especially raffinose series OSs (RSOs) are hypothesized to play an important role in the acquisition of desiccation tolerance and consequently in seed storability. In the present work we analyzed the seed-soluble OS (sucrose, raffinose, and stachyose) content of several Arabidopsis accessions and thus identified the genotype Cape Verde Islands having a very low RSO content. By performing quantitative trait loci (QTL) mapping in a recombinant inbred line population, we found one major QTL responsible for the practically monogenic segregation of seed stachyose content. This locus also affected the content of the two other OSs, sucrose, and raffinose. Two candidate genes encoding respectively for galactinol synthase and raffinose synthase were located within the genomic region around this major QTL. In addition, three smaller-effect QTL were identified, each one specifically affecting the content of an individual OS. Seed storability was analyzed in the same recombinant inbred line population by measuring viability (germination) under two different seed aging assays: after natural aging during 4 years of dry storage at room temperature and after artificial aging induced by a controlled deterioration test. Thus, four QTL responsible for the variation of this trait were mapped. Comparison of the QTL genetic positions showed that the genomic region containing the major OS locus did not significantly affect the seed storability. We concluded that in the studied material neither RSOs nor sucrose content had a specific effect on seed storability.

Arabidopsis↗

Creating a saturated reference map for the apple (Malus x domestica Borkh.) genome.

The availability of a high quality linkage map is essential for the detection and the analysis of quantitative traits. Such a map should cover a significant part of the genome, should be densely populated with markers, and in order to gain the maximum advantage should be transferable to populations or cultivars other than the ones on which it has been constructed. An apple genetic linkage map has been constructed on the basis of a segregating population of the cross between the cultivars Fiesta and Discovery. A total of 840 molecular markers, 475 AFLPs, 235 RAPDs, 129 SSRs and 1 SCAR, were used for the two parental maps constructed with JoinMap and spanning 1,140 cM and 1,450 cM, respectively. Large numbers of codominant markers, like SSRs, enable a rapid transfer of the map to other populations or cultivars, allowing the investigation of any chosen trait in another genetic background. This map is currently the most advanced linkage map in apple with regard to genome coverage and marker density. It represents an ideal starting point for future mapping projects in Malus since the stable and transferable SSR frame of the map can be saturated quickly with dominant AFLP markers.

Automation↗

[Molecular mapping of QTLs for rice milling yield traits].

QTLs of three milling yield traits, including brown rice (BR,%), milled rice (MR,%) and head milled rice (HR,%), were mapped using a set of 212 Lemont/Teqing RI population, an RFLP linkage map with 182 markers and a mixed model approach(QTLMapper V1.0). The population showed continuous distributions with transgressive segregation on both sides for all traits while HR had a wider variation than BR and MR. One and four main effect QTLs were detected for MR and HR. Two QTLs for HR(QHr6 and QHr7) had large additive effects. Twelve, five and sixteen pairs of digenic epistatic loci were associated with BR, MR and HR respectively. Epistasis was more important than main effect QTLs according to the mapping result. A complex relationship was observed for epistatic pairs mapped in same trait or among different traits by sharing intervals.

Chromosome Mapping↗

Studies of natural allele effects in mice can be used to identify genes causing common human obesity.

Although genes causing rare Mendelian forms of human obesity have provided much useful information about underlying causes of obesity, these genes do not explain significant proportions of common obesity. This review presents evidence that animal models can be used to uncover subtle genetic effects on obesity and can provide a powerful rigorous compliment to human association studies. We discuss the advantages of animal models of obesity, various approaches to discovering obesity genes, and the future of mapping and isolating naturally occurring alleles of obesity genes. We review evidence that it is important to map naturally occurring obesity genes using quantitative trait locus (QTL) mapping, instead of mutagenesis and knockout models because the latter do not allow study of interactions and because naturally occurring obesity alleles can interfere with cloning from mutagenesis projects. Because a substantial percentage of human obesity results from complex interactions, the underlying genes can only be identified by direct studies in humans, which are still very difficult, or by studies in mice that begin with QTL mapping. Finally, we emphasize that animal model studies can be used to prove that a specific gene, only associated with obesity in humans, can indeed be the underlying cause of obesity in mammals.

Animals↗

Molecular tagging of erucic acid trait in oilseed mustard (Brassica juncea) by QTL mapping and single nucleotide polymorphisms in FAE1 gene.

Molecular mapping and tagging of the erucic acid trait (C22:1) in Brassica juncea was done by a candidate gene approach. Two QTLs underlying the variation of seed erucic acid content were assigned to two linkage groups of a B. juncea map using a doubled haploid (DH) mapping population derived from high x low erucic acid F(1) hybrid. Two consensus primers corresponding to the full-length Fatty Acid Elongase 1 ( FAE1) gene, reported to be involved in the elongation of C18:1 to C22:1, were designed. PCR amplification and subsequent cloning and sequencing identified two FAE1 genes ( FAE1.1 and FAE1.2) in both high and low erucic acid mustard lines. Sequence alignment of corresponding FAE1 genes between high and low erucic acid mustard lines identified four substitution type single nucleotide polymorphisms (SNPs) in FAE1.1 and three in FAE1.2. Using the SNuPE method of SNP genotyping, these two genes were mapped to two independent loci that co-segregated with the two QTLs governing the erucic acid trait. Association of wild ( E1E2) and mutant ( e1e2) haplotypes of two FAE1 genes with erucic acid variation in two segregating populations revealed that the e1e1e2e2 genotype identified low erucic acid individuals (<2%) and E1E1E2E2 identified individuals with highest erucic acid content (>40%). The E1e1E2e2 heterozygote was found to be intermediate in phenotype. The applicability of these SNPs in marker-assisted manipulation of the erucic acid trait was verified by genotyping a set of contrasting germplasm of B. juncea belonging to two distinct gene pools (Indian and east European) and other oil-yielding Brassica species.

Acetyltransferases↗

QTL mapping for seed vigor-related traits under artificial aging in common wheat in two introgression line (IL) populations.

BACKGROUND: Seed vigor recognized as a quantitative trait is of particular importance for agricultural production. However, limited knowledge is available for understanding genetic basis of wheat seed vigor. METHODS: The aim of this study was to identify quantitative trait loci (QTL) responsible for 10 seed vigor-related traits representing multiple aspects of seed-vigor dynamics during artificial aging with 6 different treatment times (0, 24, 36, 48, 60, and 72 h) under controlled conditions (48&#xa0;&#xb0;C, 95% humidity, and dark). The mapping populations were two wheat introgression lines (IL-1 and IL-2) derived from recipient parent (Lumai 14) and donor parent (Shaanhan 8675 or Jing 411). RESULTS: A total of 26 additive QTLs and 72 pairs of epistatic QTLs were detected for wheat seed-vigor traits. Importantly, chromosomes 1B and 7B contained several co-located QTLs, and chromosome 2A had a QTL-rich region near the marker Xwmc667, indicating that these QTLs may affect wheat seed vigor with pleiotropic effects. Furthermore, several possible consistent QTLs (hot-spot regions) were examined by comparison analysis of QTLs detected in this study and reported previously. Finally, a set of candidate genes for wheat seed vigor were predicted to be involved in transcription regulation, carbohydrate and lipid metabolism. CONCLUSION: The present findings lay new insights into the mechanism underlying wheat seed vigor, providing valuable information for wheat genetic improvement especially marker-assisted breeding to increase seed vigor and consequently achieve high grain yield despite of further investigation required.

Triticum↗

Cotton genome mapping with new microsatellites from Acala 'Maxxa' BAC-ends.

Fine mapping and positional cloning will eventually improve with the anchoring of additional markers derived from genomic clones such as BACs. From 2,603 new BAC-end genomic sequences from Gossypium hirsutum Acala 'Maxxa', 1,316 PCR primer pairs (designated as MUSB) were designed to flank microsatellite or simple sequence repeat motif sequences. Most (1164 or 88%) MUSB primer pairs successfully amplified DNA from three species of cotton with an average of three amplicons per marker and 365 markers (21%) were polymorphic between G. hirsutum and G. barbadense. An interspecific RIL population developed from the above two entries was used to map 433 marker loci and 46 linkage groups with a genetic distance of 2,126.3 cM covering approximately 45% of the cotton genome and an average distance between two loci of 4.9 cM. Based on genome-specific chromosomes identified in G. hirsutum tetraploid (A and D), 56.9% of the coverage was located on the A subgenome while 39.7% was assigned to the D subgenome in the genetic map, suggesting that the A subgenome may be more polymorphic and recombinationally active than originally thought. The linkage groups were assigned to 23 of the 26 chromosomes. This is the first genetic map in which the linkage groups A01 and A02/D03 have been assigned to specific chromosomes. In addition the MUSB-derived markers from BAC-end sequences markers allows fine genetic and QTL mapping of important traits and for the first time provides reconciliation of the genetic and physical maps. Limited QTL analyses suggested that loci on chromosomes 2, 3, 12, 15 and 18 may affect variation in fiber quality traits. The original BAC clones containing the newly mapped MUSB that tag the QTLs provide critical DNA regions for the discovery of gene sequences involved in biological processes such as fiber development and pest resistance in cotton.

Chromosomes, Artificial, Bacterial↗

High-density mapping and comparative analysis of agronomically important traits on wheat chromosome 3A.

Bread wheat chromosome 3A has been shown to contain genes/QTLs controlling grain yield and other agronomic traits. The objectives of this study were to generate high-density physical and genetic-linkage maps of wheat homoeologous group 3 chromosomes and reveal the physical locations of genes/QTLs controlling yield and its component traits, as well as agronomic traits, to obtain a precise estimate of recombination for the corresponding regions and to enrich the QTL-containing regions with markers. Physical mapping was accomplished by 179 DNA markers mostly representing expressed genes using 41 single-break deletion lines. Polymorphism survey of cultivars Cheyenne (CNN) and Wichita (WI), and a substitution line of CNN carrying chromosome 3A from WI [CNN(WI3A)], with 142 RFLP probes and 55 SSR markers revealed that the extent of polymorphism is different among various group 3 chromosomal regions as well as among the homoeologs. A genetic-linkage map for chromosome 3A was developed by mapping 17 QTLs for seven agronomic traits relative to 26 RFLP and 15 SSR chromosome 3A-specific markers on 95 single-chromosome recombinant inbred lines. Comparison of the physical maps with the 3A genetic-linkage map localized the QTLs to gene-containing regions and accounted for only about 36% of the chromosome. Two chromosomal regions containing 9 of the 17 QTLs encompassed less than 10% of chromosome 3A but accounted for almost all of the arm recombination. To identify rice chromosomal regions corresponding to the particular QTL-containing wheat regions, 650 physically mapped wheat group 3 sequences were compared with rice genomic sequences. At an E value of E < or = 10(-5), 82% of the wheat group 3 sequences identified rice homologs, of which 54% were on rice chromosome 1. The rice chromosome 1 region collinear with the two wheat regions that contained 9 QTLs was about 6.5 Mb.

Chromosome Mapping↗

Genetic and molecular dissection of naturally occurring variation.

Recent progress in plant genome analysis has made it possible to examine the naturally occurring allelic variation underlying complex traits. Many studies have described the genetic mapping of quantitative trait loci for several kinds of complex phenotypic traits. Some researchers have taken up the challenge of performing the molecular cloning of genes at these loci, and examples of cloning have recently been reported. Naturally occurring allelic variation could be a new resource for the functional analysis of plant genes.

Alleles↗

High-resolution patterns of meiotic recombination across the human major histocompatibility complex.

Definitive characteristics of meiotic recombination events over large (i.e., >1 Mb) segments of the human genome remain obscure, yet they are essential for establishing the haplotypic structure of the genome and for efficient mapping of complex traits. We present a high-resolution map of recombination at the kilobase level across a 3.3-Mb interval encompassing the major histocompatibility complex (MHC). Genotyping of 20,031 single sperm from 12 individuals resulted in the identification and fine mapping of 325 recombinant chromosomes within genomic intervals as small as 7 kb. Several principal characteristics of recombination in this region were observed: (1) rates of recombination can differ significantly between individuals; (2) intense hot spots of recombination occur at least every 0.8 Mb but are not necessarily evenly spaced; (3) distribution in the location of recombination events can differ significantly among individuals; (4) between hot spots, low levels of recombination occur fairly evenly across 100-kb segments, suggesting the presence of warm spots of recombination; and (5) specific sequence motifs associate significantly with recombination distribution. These data provide a plausible model for recombination patterns of the human genome overall.

Adolescent↗

Estimating linkage disequilibrium between a polymorphic marker locus and a trait locus in natural populations.

Positional cloning of gene(s) underlying a complex trait requires a high-resolution linkage map between the trait locus and genetic marker loci. Recent research has shown that this may be achieved through appropriately modeling and screening linkage disequilibrium between the candidate marker locus and the major trait locus. A quantitative genetics model was developed in the present study to estimate the coefficient of linkage disequilibrium between a polymorphic genetic marker locus and a locus underlying a quantitative trait as well as the relevant genetic parameters using the sample from randomly mating populations. Asymptotic covariances of the maximum-likelihood estimates of the parameters were formulated. Convergence of the EM-based statistical algorithm for calculating the maximum-likelihood estimates was confirmed and its utility to analyze practical data was exploited by use of extensive Monte-Carlo simulations. Appropriateness of calculating the asymptotic covariance matrix in the present model was investigated for three different approaches. Numerical analyses based on simulation data indicated that accurate estimation of the genetic parameters may be achieved if a sample size of 500 is used and if segregation at the trait locus explains not less than a quarter of phenotypic variation of the trait, but the study reveals difficulties in predicting the asymptotic variances of these maximum-likelihood estimates. A comparison was made between the statistical powers of the maximum-likelihood analysis and the previously proposed regression analysis for detecting the disequilibrium.

Genetic Markers↗

Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci.

Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.

Animals↗

Quantitative trait loci for floral morphology in Arabidopsis thaliana.

A central question in biology is how genes control the expression of quantitative variation. We used statistical methods to estimate genetic variation in eight Arabidopsis thaliana floral characters (fresh flower mass, petal length, petal width, sepal length, sepal width, long stamen length, short stamen length, and pistil length) in a cosmopolitan sample of 15 ecotypes. In addition, we used genome-wide quantitative trait locus (QTL) mapping to evaluate the genetic basis of variation in these same traits in the Landsberg erecta x Columbia recombinant inbred line population. There was significant genetic variation for all traits in both the sample of naturally occurring ecotypes and in the Ler x Col recombinant inbred line population. In addition, broad-sense genetic correlations among the traits were positive and high. A composite interval mapping (CIM) analysis detected 18 significant QTL affecting at least one floral character. Eleven QTL were associated with several floral traits, supporting either pleiotropy or tight linkage as major determinants of flower morphological integration. We propose several candidate genes that may underlie these QTL on the basis of positional information and functional arguments. Genome-wide QTL mapping is a promising tool for the discovery of candidate genes controlling morphological development, the detection of novel phenotypic effects for known genes, and in generating a more complete understanding of the genetic basis of floral development.

Arabidopsis↗

Quantitative trait loci affecting risk for pentobarbital withdrawal map near alcohol withdrawal loci on mouse chromosomes 1, 4, and 11.

Barbiturate dependence is associated with the development of physiological dependence (withdrawal), tolerance, or a maladaptive pattern of drug use. Analysis of strain and individual differences with animal models for physiological dependence liability are useful means to identify potential genetic determinants of liability in humans. Behavioral and quantitative trait locus (QTL) mapping analyses were conducted with mice that are resistant versus sensitive to pentobarbital withdrawal. With a multistage genetic mapping strategy, a pentobarbital withdrawal QTL (Pbw1) was mapped to the distal region of mouse Chromosome (Chr) 1 and may be identical to an alcohol withdrawal QTL mapped to this chromosomal region. Two suggestive QTLs for pentobarbital withdrawal, both in proximity to QTLs definitely mapped for alcohol withdrawal, were also tentatively identified. These were on Chr 11 in proximity to a gene cluster including several members of the GABAA receptor gene family, and on Chr 4 near a locus associated with beta-carboline-induced seizure severity. These data represent the first detection and mapping of loci influencing risk for physiological dependence on barbiturates, and suggest the involvement of common genes in physiological dependence on pentobarbital and alcohol.

Animals↗

Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics.

This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and analyses of divergent and complex traits. This strain, derived by crossing the spontaneously hypertensive rat, SHR/Ola, with a Brown Norway congenic, BN-Lx, carrying polydactyly-luxate syndrome, is referred to as HXB/BXH. The RI strain set has been used for linkage and association studies to identify quantitative trait loci for numerous cardiovascular phenotypes, including arterial pressure, stress-elicited heart rate, and pressor response, and metabolic traits, including insulin resistance, dyslipidemia and glucose handling, and left ventricular hypertrophy. The strain's utility has been enhanced with development of a new framework marker-based map and strain distribution patterns of polymorphic markers. Quantitative trait loci for behavioral traits mapped include loci for startle motor response and habituation, anxiety and locomotion traits associated with elevated plus maze, and conditioned taste aversion. The polydactyly-luxate syndrome Lx mutation has allowed the study of alleles important to limb development and malformation phenotypes as well as teratogens. The RI strains have guided development of numerous congenic strains to test locus assignments and to study the effect of genetic background. Although these strains were originally developed to aid in studies of rat genetic hypertension and morphogenetic abnormalities, this rodent platform has been shown to be equally powerful for a wide spectrum of traits and endophenotypes. These strains provide a ready and available vehicle for many physiological and pharmacological studies.

Animals↗

Substitution mapping of a blood pressure quantitative trait locus to a 2.73 Mb region on rat chromosome 1.

OBJECTIVE: To improve the localization of a blood pressure quantitative trait locus (BP QTL) on rat chromosome (RNO) 1. METHODS: Congenic substrains were derived from the progenitor congenic strains S.LEW(D1Mco4X1) and S.LEW(D1Mco4X5) which previously localized a BP QTL (region 2) to a 17cM interval on RNO1. The newly developed congenic substrains, along with control Dahl salt-sensitive (S) rats were fed a 2% NaCl diet for 24 days before their BP was compared by both tail-cuff and radiotelemetry methods. RESULTS: By comparing BP of these congenic substrains to that of S rats, we have refined the location of the BP QTL2 region to a 2.73 Mb genomic interval that contains 19 annotated genes in the latest rat genome assembly (version 2.1). Slc9a3, the gene encoding the Na(+)/H(+) exchanger 3, originally a candidate gene in the BP QTL2 region, is excluded based on its map location. CONCLUSION: Substitution mapping was used to reduce a BP QTL on RNO1 from 17 centimorgans (cM) to approximately 1.4 cM (= 2.73 Mb). This region now contains 19 annotated rat candidate genes.

Animals↗