Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “quantitative trait”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,459 records · Page 81Linked to original sources

Estimating effects of a single gene and polygenes on quantitative traits from a diallel design.

A genetic model is developed with additive and dominance effects of a single gene and polygenes as well as general and specific reciprocal effects for the progeny from a diallel mating design. The methods of ANOVA, minimum norm quadratic unbiased estimation (MINQUE), restricted maximum likelihood estimation (REML), and maximum likelihood estimation (ML) are suggested for estimating variance components, and the methods of generalized least squares (GLS) and ordinary least squares (OLS) for fixed effects, while best linear unbiased prediction, linear unbiased prediction (LUP), and adjusted unbiased prediction are suggested for analyzing random effects. Monte Carlo simulations were conducted to evaluate the unbiasedness and efficiency of statistical methods involving two diallel designs with commonly used sample sizes, 6 and 8 parents, with no and missing crosses, respectively. Simulation results show that GLS and OLS are almost equally efficient for estimation of fixed effects, while MINQUE (1) and REML are better estimators of the variance components and LUP is most practical method for prediction of random effects. Data from a Drosophila melanogaster experiment (Gilbert 1985a, Theor appl Genet 69:625-629) were used as a working example to demonstrate the statistical analysis. The new methodology is also applicable to screening candidate gene(s) and to other mating designs with multiple parents, such as nested (NC Design I) and factorial (NC Design II) designs. Moreover, this methodology can serve as a guide to develop new methods for detecting indiscernible major genes and mapping quantitative trait loci based on mixture distribution theory. The computer program for the methods suggested in this article is freely available from the authors.

Alleles↗

Quantitative trait loci mapping for meat quality and muscle fiber traits in a Japanese wild boar x Large White intercross.

Three generations of a swine family produced by crossing a Japanese wild boar and three Large White female pigs were used to map QTL for various production traits. Here we report the results of QTL analyses for skeletal muscle fiber composition and meat quality traits based on phenotypic data of 353 F(2) animals and genotypic data of 225 markers covering almost the entire pig genome for all of the F(2) animals as well as their F(1) parents and F(0) grandparents. The results of a genome scan using least squares regression interval mapping provided evidence that QTL (<1% genome-wise error rate) affected the proportion of the number of type IIA muscle fibers on SSC2, the number of type IIB on SSC14, the relative area (RA) of type I on SSCX, the RA of type IIA on SSC6, the RA of type IIB on SSC6 and SSC14, the Minolta a* values of loin on SSC4 and SSC6, the Minolta b* value of loin on SSC15, and the hematin content of the LM on SSC6. Quantitative trait loci (<5% genome-wise error rate) were found for the number of type I on SSC1, SSC14, and SSCX, for the number of type IIA on SSC14, for the number of type IIB on SSC2, for the RA of type IIA on SSC2, for the Minolta b* value of loin on SSC3, for the pH of loin on SSC15, and for the i.m. fat content on SSC15. Twenty-four QTL were detected for 11 traits at the 5% genome-wise level. Some traits were associated with each other, so the 24 QTL were located on 11 genomic regions. In five QTL located on SSC2, SSC6, and SSC14, each wild boar allele had the effect of increasing types I and IIA muscle fibers and decreasing type IIB muscle fibers. These effects are expected to improve meat quality.

Animals↗

Mapping of quantitative trait loci determining NK cell-mediated resistance to MHC class I-deficient bone marrow grafts in perforin-deficient mice.

NK cells reject allogeneic and MHC class I-deficient bone marrow (BM) grafts in vivo. The mechanisms used by NK cells to mediate this rejection are not yet thoroughly characterized. Although perforin plays a major role, perforin-independent mechanisms are involved as well. C57BL/6 mice deficient in perforin (B6 perforin knockout (PKO)) reject class I-deficient TAP-1 KO BM cells as efficiently as normal B6 mice. In contrast, perforin-deficient 129S6/SvEvTac mice (129 PKO) cannot mediate this rejection while normal 129 mice efficiently reject. This suggests that in 129, but not in B6, mice, perforin is crucial for NK cell-mediated rejection of MHC class I-deficient BM grafts. To identify loci linked to BM rejection in perforin-deficient mice, we generated backcross 1 progeny by crossing (129 x B6)F(1) PKO mice to 129 PKO mice. In transplantation experiments, >350 backcross 1 progeny were analyzed and displayed a great variation in ability to reject TAP-1 KO BM grafts. PCR-based microsatellite mapping identified four quantitative trait loci (QTL) on chromosomes 2, 4, and 8, with the QTL on chromosome 8 showing the highest significance, as well as a fifth epistatic QTL on chromosome 3. This study describes the first important step toward identifying BM graft resistance gene(s).

Animals↗

Mapping of a quantitative trait locus for morphine withdrawal severity.

Chronic morphine exposure results in physical dependence, manifested by physical symptoms during naloxone-precipitated withdrawal. Jumping frequency is widely considered the most sensitive and reliable index of withdrawal intensity in mice. Inbred mouse strains surveyed for naloxone-precipitated withdrawal display large and significant strain differences in jumping frequency, including an approximately tenfold difference between C57BL/6 and 129P3 mice. In the present study, (B6 x 129)F2 hybrid mice were given daily morphine injections for four days using an escalating dosing schedule, and naloxone-precipitated withdrawal on day 5 was measured. A full-genome scan for linkage to phenotypic data was performed using polymorphic microsatellite markers. Significant linkage was observed between withdrawal jumping frequencies and a 28 cM-wide region of Chromosome 1 (32-60 cM; peak at 51 cM), accounting for 20% of the overall phenotypic variance. Two other suggestive QTLs were found, on Chromosomes 5 and 10, and an additive model fitting all three loci accounted for 43% of the total variance. F2 mice were also assessed for changes in morphine analgesic potency using the tail-withdrawal test in dose-response studies on days 1 and 4. No linkage was observed between Chromosomes 1, 5, and 10 and morphine analgesic tolerance, suggestive of genetic dissociation of naloxone-precipitated withdrawal from morphine and chronic morphine intake per se. The significant quantitative trait locus for naloxone-precipitated withdrawal severity in morphine-dependent mice, which we name Depmq1, may prove to be of considerable heuristic value once the underlying gene or genes are identified.

Analgesics, Opioid↗

Identification of quantitative trait loci and associated candidate genes for low-temperature tolerance in cold-hardy winter wheat.

Low-temperature (LT) tolerance is an important economic trait in winter wheat (Triticum aestivum L.) that determines the plants' ability to cope with below freezing temperatures. Essential elements of the LT tolerance mechanism are associated with the winter growth habit controlled by the vernalization loci (Vrn-1) on the group 5 chromosomes. To identify genomic regions, which in addition to vrn-1 determine the level of LT tolerance in hexaploid wheat, two doubled haploid (DH) mapping populations were produced using parents with winter growth habit (vrn-A1, vrn-B1, and vrn-D1) but showing different LT tolerance levels. A total of 107 DH lines were analyzed by genetic mapping to produce a consensus map of 2,873 cM. The LT tolerance levels for the Norstar (LT(50)=-20.7 degrees C) x Winter Manitou (LT(50)=-14.3 degrees C) mapping population ranged from -12.0 to -22.0 degrees C. Single marker analysis and interval mapping of phenotyped lines revealed a major quantitative trait locus (QTL) on chromosome 5A and a weaker QTL on chromosome 1D. The 5A QTL located 46 cM proximal to the vrn-A1 locus explained 40% of the LT tolerance variance. Two C-repeat Binding Factor (CBF) genes expressed during cold acclimation in Norstar were located at the peak of the 5A QTL.

Cold Temperature↗

Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry.

We recently conducted a dose-response study of the effects of cocaine on several activity measures in the panel of BxD/Ty recombinant inbred mice. Animals were tested in an automated activity chamber over 2 days with i.p. saline on day 1 and i.p. cocaine on day 2, at one of four doses, 5, 15, 30 or 45 mg kg(-1). The monitor recorded total distance traveled, nosepokes in a holeboard, repeated movements and time spent by an individual in proximity to the centre of the apparatus. Dose-response curves for locomotor activation, i.e. the difference between cocaine and saline scores, showed that for all strains tested, scores increased 5-30 mg kg(-1). With few exceptions, locomotor activity at 45 mg kg(-1) was not significantly higher than that at 30 mg kg(-1). Repeated movement scores showed patterns similar to locomotor activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all behaviours and at all doses exhibited continuous, rather than discrete variation, thus providing evidence of multiple-gene effects on cocaine-related behaviours. Quantitative trait loci (QTL) analysis pointed to several chromosomal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate groups of animals, densities of dopamine D1, and D2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. In all areas, all measures showed distributions consistent with polygenic influence and were associated with QTL. Of particular interest was our finding of a large segment on chromosome 15, which is related to dopamine receptor densities and cocaine-related behaviours.

Animals↗

Genetic control of susceptibility to UV-induced immunosuppression by interacting quantitative trait loci.

Ultraviolet B radiation (290-320 nm) initiates a dose and wavelength dependent down-regulation of cell-mediated immunity which is critical in experimental ultraviolet radiation (UV) carcinogenesis, preventing immune attack on highly antigenic UV-induced tumors. UV-induced immunosuppression has been demonstrated in humans and may be a risk factor for skin cancer. In this study, we have investigated genetic linkage of the autosomal loci controlling this trait. Previously, we had derived a model describing control of susceptibility to UV-induced immunosuppression in inbred mice by unlinked interacting autosomal and X-linked loci. A genome-wide scan using MIT microsatellite markers was carried out on 100 backcross (BALB/c x (BALB/c x C57BL/6) F1) mice derived from the inbred strains BALB/c (low susceptibility) and C57BL/6 (high susceptibility) and tested for systemic UV-induced immunosuppression of a contact hypersensitivity response. The values for % suppression for each animal and the genotype data were used to investigate genetic linkage by multiple regression analysis. Significance was assessed using the permutation test. Both main effects and interactive effects were investigated, first with each genotype marker singly, and secondly, in a novel approach using markers pairwise. A joint model was derived in which all loci and pairs of loci identified were included simultaneously in a multiple regression model. This model indicates four quantitative trait loci (QTLs) with significant main effects, one on chromosome 10 which decreased susceptibility to UV-induced immunosuppression and QTLs on chromosomes 6, 17 and 1 which increased susceptibility. Additionally, loci on chromosomes 14 and 19 showed significant interaction with the locus on chromosome 1. Further investigation indicated a potential three-way interaction involving the loci on chromosomes 1, 14 and 19.

Animals↗

Evidence for a major quantitative trait locus on chromosome 17q21 affecting low-density lipoprotein peak particle diameter.

BACKGROUND: Several lines of evidence suggest that small dense LDL particles are associated with the risk of coronary heart disease. Heritability and segregation studies suggest that LDL particle size is characterized by a large genetic contribution and the presence of a putative major genetic locus. However, association and linkage analyses have thus far been inconclusive in identifying the underlying gene(s). METHODS AND RESULTS: An autosomal genome-wide scan for LDL peak particle diameter (LDL-PPD) was performed in the Québec Family Study. A total of 442 markers were genotyped, with an average intermarker distance of 7.2 cM. LDL-PPD was measured by gradient gel electrophoresis in 681 subjects from 236 nuclear families. Linkage was tested by both sib-pair-based and variance components-based linkage methods. The strongest evidence of linkage was found on chromosome 17q21.33 at marker D17S1301, with an LOD score of 6.76 by the variance-components method for the phenotype adjusted for age, body mass index, and triglyceride levels. Similar results were obtained with the sib-pair method (P<0.0001). Other chromosomal regions harboring markers with highly suggestive evidence of linkage (P< or =0.0023; LOD > or =1.75) include 1p31, 2q33.2, 4p15.2, 5q12.3, and 14q31. Several candidate genes are localized under the peak linkages, including apolipoprotein H on chromosome 17q, the apolipoprotein E receptor 2, and members of the phospholipase A2 family on chromosome 1p as well as HMG-CoA reductase on chromosome 5q. CONCLUSIONS: This genome-wide scan for LDL-PPD indicates the presence of a major quantitative trait locus located on chromosome 17q and others interesting loci influencing the phenotype.

Adult↗

Identification of quantitative trait loci for cardiac hypertrophy in two different strains of the spontaneously hypertensive rat.

Cardiac hypertrophy and left ventricular hypertrophy are known to be substantially controlled by genetic factors. As an experimental model, we undertook genome-wide screens for cardiac mass in F2 populations bred from the stroke-prone spontaneously hypertensive rats (SHRSP) and normal spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) of a Japanese colony. Two F2 cohorts were independently produced: F2(SHRSP x WKY) (110 male and 110 female rats) and F2(SHR x WKY) (151 male rats). The ratio of heart weight to body weight (Hw/Bw) was evaluated at 12 months of age in F2(SHRSP x WKY) after salt-loading for 7 months, and at around 15 weeks of age in F2(SHR x WKY) who had been fed a normal rat chow diet. Subsequent to an initial screen with 251 markers in F2(SHRSP x WKY) male progeny, 170 and 161 markers were selected and characterized in F2(SHRSP x WKY) female progeny and F2(SHR x WKY) male progeny, respectively. Markers from four chromosomal regions showed suggestive or significant linkage to Hw/Bw. The strongest and the most consistent linkage was found in the vicinity of D3Mgh16 on rat chromosome (RNO) 3 (a maximal log of the odds score reached 4.0 to 6.6 across the F2 populations studied). In the other three regions on RNO6, RNO10 and RNO13, the degree of linkage was more prominent in either males or females. These data provide solid evidence for a "principal" RNO3 quantitative trait loci regulating Hw/Bw in SHRSP and SHR, and also suggest the possible presence of sexual dimorphism in regard to genetic susceptibility for cardiac hypertrophy.

Animals↗

In silico quantitative trait locus map for atherosclerosis susceptibility in apolipoprotein E-deficient mice.

OBJECTIVE: Atherosclerosis susceptibility is a genetic trait that varies between mouse strains. The goal of this study was to use a public mouse single nucleotide polymorphism (SNP) database to define the genetic loci that are associated with this trait, without the need to perform strain intercrosses that are normally required to obtain these loci. METHODS AND RESULTS: Apolipoprotein E (apoE)-deficient mice on 6 inbred genetic backgrounds were compared for atherosclerosis lesion size in the aortic root in 2 independent studies. After normalization to the C57BL/6 strain that was used in both studies, lesion areas were found in the following rank order: DBA/2J>C57BL/6>129/SV-ter>AKR/J approximately BALB/cByJ approximately C3H/HeJ. The log lesion difference in phenotypes between each of the 15 heterologous strain pairs was determined. A mouse SNP database was then used to calculate the genetic differences between the 15 strain pairs in partially overlapping 30-cM bins across the mouse genome. Correlation analyses were preformed to analyze the genetic and phenotypic differences among the strain pairs for each genetic region. The genetic regions with the highest correlations define the in silico quantitative trait loci (QTL) associated with the atherosclerosis phenotype. Five in silico atherosclerosis QTL were identified on chromosomes 1, 10, 14, 15, and 18. The loci on chromosomes 1, 10, 14, and 18 overlap with suggestive atherosclerosis QTL identified through analyses of an F(2) cohort derived from apoE-deficient mice on the C57BL/6 and FVB/N strains. CONCLUSIONS: The 5 identified in silico QTL are candidates for further study to confirm the presence and identity of atherosclerosis susceptibility genes within these loci.

Animals↗

Quantitative trait loci for hypercalciuria in a rat model of kidney stone disease.

Hypercalciuria is the most common risk factor for kidney stones and has a recognized familial component. The genetic hypercalciuric stone-forming (GHS) rat is an animal model that closely resembles human idiopathic hypercalciuria, with excessive intestinal calcium absorption, increased bone resorption, and impaired renal calcium reabsorption; overexpression of the vitamin D receptor (VDR) in target tissues; and calcium nephrolithiasis. For identifying genetic loci that contribute to hypercalciuria in the GHS rat, an F2 generation of 156 rats bred from GHS female rats and normocalciuric WKY male rats was studied. The calcium excretion was six- to eightfold higher in the GHS female than in the WKY male progenitors. Selective genotyping of those F2 rats with the highest 30% and lowest 30% rates of calcium excretion was performed, scoring 98 markers with a mean interval of 23 cM across all 20 autosomes and the X chromosome. With the use of strict criteria for significance, significant linkage was found between hypercalciuria and a region of chromosome 1 at D1Rat169 (LOD, 2.91). Suggestive linkage to regions of chromosomes 4, 7, 10, and 14 was found. The proportion of phenotypic variance contributed by the region on chromosome 1, with appropriate adjustments, was estimated to be 7%. Candidate genes encoding the VDR and the calcium-sensing receptor were localized to regions on rat chromosomes 7 and 11, respectively, but the suggestive quantitative trait locus on chromosome 7 was not in the region of the VDR gene locus. Identification of genes that contribute to hypercalciuria in this animal model should prove valuable in understanding idiopathic hypercalciuria and kidney stone disease in humans.

Animals↗

Identification of quantitative trait loci for glucose homeostasis: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study.

Genetic and environmental determinants play critical roles in insulin resistance and beta-cell function. A model of the complex feedback system for maintenance of glucose tolerance has been developed that reflects the constraint of glycemia within narrow physiologic limits. The "glucose homeostasis" model is described by insulin sensitivity (S(I)), glucose disposition (S(G)), acute insulin response to glucose (AIR(G)), and disposition index (DI). Relatively little is known about the genetic basis of glucose homeostasis phenotypes or their relationship to risk of diabetes and atherosclerotic cardiovascular disease. A genome scan for glucose homeostasis phenotypes in nondiabetic subjects has been carried out in African-American (n = 21) and Hispanic (n = 45) extended families as part of the IRAS Family Study. In African-American families, there was significant evidence for linkage of DI between D11S2371 and D11S2002 (logarithm of odds [LOD] = 3.21) at 81 cM, and in the combined sample of African-American and Hispanic families, there was evidence at GATA117D01 (140 cM) on chromosome 11 (LOD = 2.21). Evidence of linkage was also observed for S(I) in Hispanic (LOD = 2.28, between D15S822 and GTTTT001) and AIR(G) in African-American families (LOD = 2.73, between D4S1625 and D4S1629; and LOD = 2.56 at PAH (phenylalanine hydroxylase) on chromosome 12). These results provide impetus for future positional cloning of quantitative trait loci (QTLs). Identifying genes in these regions should provide insight into the nature of the metabolic syndrome and diabetes, and facilitate the development of more effective therapies for prevention and treatment of diabetes and other diseases associated with disordered glucose metabolism.

Adult↗

Quantitative trait loci for BMD identified by autosome-wide linkage scan to chromosomes 7q and 21q in men from the Amish Family Osteoporosis Study.

UNLABELLED: Using autosome-wide linkage analysis in 964 Amish, strong evidence was found for the presence of genes affecting hip and spine BMD in men on chromosomes 7q31 and 21q22 (LOD = 4.15 and 3.36, respectively). INTRODUCTION: BMD is highly heritable, with genetic factors accounting for 60-88% of variation. The goal of this study was to localize genes contributing to BMD variation. MATERIALS AND METHODS: The Amish Family Osteoporosis Study was designed to identify genes affecting bone health. The Amish are a genetically closed population with a homogeneous lifestyle. BMD was measured at the spine, hip, and radius using DXA in 964 participants (mean age, 50.2 +/- 16.3 [SD] years; range, 18-99 years) from large multigenerational families. Genotyping of 731 highly polymorphic microsatellite markers (average spacing of 5.4 cM) and autosome-wide multipoint linkage analysis were performed. RESULTS: In the overall study population, no strong evidence for linkage was detected to any chromosomal region (peak LOD: 2.11 for radius BMD on chromosome 3q26). In a subgroup analysis of men (n = 371), strong evidence was detected for a quantitative trait locus (QTL) influencing BMD variation on chromosome 7q31 at the total hip (LOD = 4.15) and femoral neck (LOD = 3.09) and for a second QTL influencing spine BMD at 21q22 (LOD = 3.36). Suggestive evidence of linkage was found in men for a QTL at 12q24 affecting total hip BMD (LOD = 2.60) and at 18p11 for femoral neck (LOD = 2.07), and in women (n = 593) at 1p36 for femoral neck BMD (LOD = 2.02) and at 1q21 for spine BMD (LOD = 2.11). In age subgroup analyses, suggestive evidence for linkage was found for those <50 years of age (n = 521) on chromosomes 11q22 and 14q23 (LODs = 2.11 and 2.16, respectively) and for those >50 years of age (n = 443) on 3p25.2 (LOD = 2.32). CONCLUSIONS: These results strongly suggest the presence of genes affecting hip and spine BMD in men on chromosomes 7q31 and 21q22. Modest evidence was found for genes affecting BMD in women on chromosomes 1p36 and 1q21 and in men at 12q24, replicating results from other populations.

Adolescent↗

Mapping quantitative trait loci using the experimental designs of recombinant inbred populations.

In the data collection of the QTL experiments using recombinant inbred (RI) populations, when individuals are genotyped for markers in a population, the trait values (phenotypes) can be obtained from the genotyped individuals (from the same population) or from some progeny of the genotyped individuals (from the different populations). Let Fu be the genotyped population and Fv (v>or=u) be the phenotyped population. The experimental designs that both marker genotypes and phenotypes are recorded on the same populations can be denoted as (Fu/Fv, u=v) designs and that genotypes and phenotypes are obtained from the different populations can be denoted as (Fu/Fv, v>u) designs. Although most of the QTL mapping experiments have been conducted on the backcross and F2(F2/F2) designs, the other (Fu/Fv, v>or=u) designs are also very popular. The great benefits of using the other (Fu/Fv, v>or=u) designs in QTL mapping include reducing cost and environmental variance by phenotyping several progeny for the genotyped individuals and taking advantages of the changes in population structures of other RI populations. Current QTL mapping methods including those for the (Fu/Fv, u=v) designs, mostly for the backcross or F2/F2 design, and for the F2/F3 design based on a one-QTL model are inadequate for the investigation of the mapping properties in the (Fu/Fv, u or=u) designs. In addition, the QTL mapping properties of the proposed and approximate methods in different designs are discussed. Simulations were performed to evaluate the performance of the proposed and approximate methods. The proposed method is proven to be able to correct the problems of the approximate and current methods for improving the resolution of genetic architecture of quantitative traits and can serve as an effective tool to explore the QTL mapping study in the system of RI populations.

Algorithms↗

Quantitative trait loci for abdominal fat and BMI in Hispanic-Americans and African-Americans: the IRAS Family study.

OBJECTIVE: To conduct linkage analysis for body mass index (BMI, kg/m2), waist-to-hip ratio (WHR), visceral adipose tissue mass (VAT, cm2) and subcutaneous adipose tissue mass (SAT, cm2) using a whole genome scan. DESIGN: Cross-sectional family study. STUDY SUBJECTS: African-American families from Los Angeles (AA, n=21 extended pedigrees) and Hispanic-American families (HA) from San Antonio, TX (HA-SA, n=33 extended pedigrees) and San Luis Valley, CO (HA-SLV, n=12 extended pedigrees), totaling 1049 individuals in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. MEASUREMENTS: VAT and SAT were measured using a computed tomography scan obtained at the fourth and fifth lumbar vertebrae. All phenotypes were adjusted for age, gender, and study center. VAT, SAT, and WHR were analyzed both unadjusted and adjusted for BMI. RESULTS: Significant linkage to BMI was found at D3S2387 (LOD=3.67) in African-Americans, and at D17S1290 in Hispanic-Americans (LOD=2.76). BMI-adjusted WHR was linked to 12q13-21 (D12S297 (LOD=2.67) and D12S1052 (LOD=2.60)) in Hispanic-Americans. The peak LOD score for BMI-adjusted VAT was found at D11S2006 (2.36) in Hispanic families from San Antonio. BMI-adjusted SAT was linked to D5S820 in Hispanic families (LOD=2.64). Evidence supporting linkage of WHR at D11S2006, VAT at D17S1290, and SAT at D1S1609, D3S2387, and D6S1056 was dependent on BMI, such that the LOD scores became nonsignificant after adjustment of these phenotypes for BMI. CONCLUSIONS: Our findings both replicate previous linkage regions and suggest novel regions in the genome that may harbor quantitative trait locis contributing to variation in measures of adiposity.

Adipose Tissue↗

Genomewide linkage scan of hand osteoarthritis in female twin pairs showing replication of quantitative trait loci on chromosomes 2 and 19.

BACKGROUND AND OBJECTIVE: Until recently, there has been little agreement between conflicting results of osteoarthritis (OA) linkage. The purpose of this study was to conduct a whole-genome linkage scan to identify susceptibility loci for idiopathic hand OA in a large, population-based sample of females. METHODS: Two OA-related radiographic phenotypes DIP (distal interphalangeal joints)-OA and Tot-KL (Kellgren-Lawrence score for both hands) chosen a priori were examined on 538 (269 pairs) monozygous and 1256 (628 pairs) dizygous (DZ) females. A genome-wide scan using microsatellite markers spaced 10 cM apart was performed on 1028 DZ twins. First, the heritability of the two OA phenotypes was estimated. Next, multipoint linkage analysis was conducted using a modified version of the Haseman-Elston method in a generalised linear model. RESULTS: Heritability for DIP-OA and Tot-KL was found to be 47.6% and 67.4%, respectively. A genome-wide scan produced reliable evidence of significant linkage of DIP-OA on chromosome 2 at 90 cM (logarithmic odds ratio (LOD) = 2.90) and for Tot-KL on chromosome 19 at 65 cM (LOD = 4.26). These results are in agreement with data published previously. Several other significant linkage peaks were observed-for example, on chromosome 1 at 250 cM and on chromosome 3 at 30 cM-but were confirmed less reliably. CONCLUSION: This is one of the largest OA linkage studies performed to date and provides clear evidence for linkage at two quantitative trait loci (on chromosome 2 at 90 cM and on chromosome 19 at 65 cM). As the results were robust and replicated in previous smaller studies, the fine mapping of these regions is a logical next step to pinpoint potential susceptibility gene(s) of interest.

Chromosome Aberrations↗

Quantitative trait loci for component physiological traits determining salt tolerance in rice.

Rice (Oryza sativa) is sensitive to salinity, which affects one-fifth of irrigated land worldwide. Reducing sodium and chloride uptake into rice while maintaining potassium uptake are characteristics that would aid growth under saline conditions. We describe genetic determinants of the net quantity of ions transported to the shoot, clearly distinguishing between quantitative trait loci (QTL) for the quantity of ions in a shoot and for those that affect the concentration of an ion in the shoot. The latter coincide with QTL for vegetative growth (vigor) and their interpretation is therefore ambiguous. We distinguished those QTL that are independent of vigor and thus directly indicate quantitative variation in the underlying mechanisms of ion uptake. These QTL independently govern sodium uptake, potassium uptake, and sodium:potassium selectivity. The QTL for sodium and potassium uptake are on different linkage groups (chromosomes). This is consistent with the independent inheritance of sodium and potassium uptake in the mapping population and with the mechanistically different uptake pathways for sodium and potassium in rice under saline conditions (apoplastic leakage and membrane transport, respectively). We report the chromosomal location of ion transport and selectivity traits that are compatible with agronomic needs and we indicate markers to assist selection in a breeding program. Based upon knowledge of the underlying mechanisms of ion uptake in rice, we argue that QTL for sodium transport are likely to act through the control of root development, whereas QTL for potassium uptake are likely to act through the structure or regulation of membrane-sited transport components.

Analysis of Variance↗