Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Trait mapping”

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 1,585 records · Page 88Linked to original sources
PubMed2003

Linkage and association between Plasmodium falciparum blood infection levels and chromosome 5q31-q33.

We have previously mapped a locus controlling Plasmodium falciparum blood infection levels (PFBI) to chromosome 5q31-q33. We genotyped 19 microsatellite markers on chromosome 5q31-q33 in a new sample of 44 pedigrees comprising 84 nuclear families and 292 individuals living in a P. falciparum endemic area. Using a nonparametric multipoint variance-component approach (by GENEHUNTER), we evidenced a peak of linkage close to D5S636 (P=0.0069), with a heritability of 0.46. Using a variance-component method for linkage-disequilibrium mapping of quantitative traits (by QTDT) and the Bonferroni correction for multiple testing, we further detected allelic association in the presence of linkage between blood infection levels and D5S487 (P=6 x 10(-5); P(c)=0.0011), which is located on the distal part of the peak. These results confirm the importance of chromosome 5q31-q33 in the genetic control of PFBI levels.

Adolescent↗
PubMed2003

Characterization of gene expression in double-muscled and normal-muscled bovine embryos.

Myostatin, a member of the transforming growth factor-beta superfamily, is a negative regulator of skeletal muscle growth. Cattle with mutations that inactivate myostatin exhibit a remarkable increase in mass of skeletal muscle called double muscling that is accompanied by an equally remarkable decrease in carcass fat. Although a mouse knockout model has been created which results in mice with a 200% increase in skeletal muscle mass, molecular mechanisms whereby myostatin regulates skeletal muscle and fat mass are not fully understood. Using suppressive subtractive hybridization, genes that were differentially expressed in double-muscled vs. normal-muscled cattle embryos were identified. Genetic variation at other loci was minimized by using embryonic samples collected from related Piedmontese x Angus dams or Belgian Blue x Hereford dams bred to a single sire of the same breed composition. Embryos were collected at 31-33 days of gestation, which is 2-4 days after high-level expression of myostatin in the developing bovine embryo. The suppressive subtraction resulted in 30 clones that were potentially differentially expressed, 19 of which were confirmed by macroarray analysis. Several of these genes have biological functions that suggest that they are directly involved in myostatin's regulation of skeletal muscle development. Furthermore, several of these genes map to quantitative trait loci known to interact with variation in the myostatin gene.

Animals↗
PubMed2002

An integrated comparative map of the porcine X chromosome.

The objectives of this study were to assign both microsatellite and gene-based markers on porcine chromosome X to two radiation hybrid (RH) panels and to develop a more extensive integrated map of SSC-X. Thirty-five microsatellite and 20 gene-based markers were assigned to T43RH, and 16 previously unreported microsatellite and 15 gene-based markers were added to IMpRH map. Of these, 30 microsatellite and 12 gene-based markers were common to both RH maps. Twenty-two gene-based markers were submitted to BLASTN analysis for identification of orthologues of genes on HSA-X. Single nucleotide polymorphisms (SNPs) were detected for 12 gene-based markers, and nine of these were placed on the genetic map. A total of 92 known loci are present on at least one porcine chromosome X map. Thirty-seven loci are present on all three maps; 31 loci are found on only one map. Location of 33 gene-based markers on the comprehensive map translates into an integrated comparative map that supports conservation of gene order between SSC-X and HSA-X. This integrated map will be valuable for selection of candidate genes for porcine quantitative trait loci (QTLs) that map to SSC-X.

Animals↗
PubMed2004

Heritability of GFR and albuminuria in Caucasians with type 2 diabetes mellitus.

BACKGROUND: Elevated urinary albumin excretion and decreased glomerular filtration rate (GFR) are risk factors for cardiovascular death and end-stage renal disease in individuals with type 2 diabetes mellitus (DM). METHODS: To determine the extent of familial aggregation of GFR and urine albumin-creatinine ratio (ACR), we calculated heritability (h2) estimates by using a variance component approach. RESULTS: Among 662 participants with DM from 310 families (422 DM-concordant sibling pairs), 51.8% (n = 343) were women, mean age was 62.3 +/- 9.2 (SD) years (median, 62.6 years), diabetes duration was 10.8 +/- 7.6 years (median, 9 years), GFR was 67.6 +/- 19.0 mL/min (median, 64.7 mL/min), and urine ACR was 139.7 +/- 631.4 mg/g (median, 13.1 mg/g). Estimated h2 of GFR was 0.75 +/- 0.10 (P < 0.0001) after adjusting for age, sex, mean arterial blood pressure, medications, and hemoglobin A(1c) level. These covariates accounted for only 2% of the total phenotypic variation in log GFR. Similarly, estimated h2 of ACR was 0.46 +/- 0.12 (P < 0.0001) when adjusting for these covariates, with covariates contributing only 9% of phenotypic variation. CONCLUSION: These data provide strong evidence that among Caucasians with type 2 diabetes, GFR and urine ACR show strong familiality, suggesting that genetic factors exhibit significant influences. Given their biological and clinical importance and the similarity of these estimates with other cardiovascular disease- and DM-related traits, efforts to map genes that influence GFR and urine ACR levels should have increased importance.

Aged↗
PubMed1999

Genetics of insulin resistance.

Even among young, healthy individuals, there is more than a 10-fold variation in insulin sensitivity; however, taken in combination, all the known modifiers of insulin sensitivity - including obesity and a variety of environmental factors - explain less than one third of this variation. It is possible that genetic factors could account for the bulk of the variance observed, and hence play a major role in the development of impaired insulin sensitivity, ie insulin resistance. From the genetic point of view, insulin resistance is thought to be due to the inheritance of a number of mutations in a variety of genes. Three complementary approaches have been applied in the search for mutations: mutational analysis of candidate genes; linkage analysis of candidate genes or chromosomal regions for insulin resistance in familial type 2 diabetes; and random genome mapping with quantitative trait loci (QTL) analysis. Mutational analysis of the insulin signalling cascade has identified a glycine-arginine (Gly-Arg) substitution at codon 972 of the insulin receptor substrate-1 (IRS-1) gene with a carrier prevalence of 9% among Caucasians. Expression of this variant in 32-D cells is associated with a significant (20-30%) impairment of insulin-stimulated PI3-kinase activity, as well as reduced binding of IRS-1 to the p85 regulatory subunit of PI3-kinase. Genotype/phenotype studies stratified according to body mass index (BMI) indicate that obese subjects who are heterozygous for the mutant allele have a 50% decrease in insulin sensitivity, compared with wild-type obese subjects. This suggests that there may be an interaction between the mutant allele and obesity, such that, in the presence of obesity, the mutant variant may aggravate the obesity-associated insulin resistance. Mutational analysis has also shown that homozygous carriers of a codon Met 326 Ile mutation in the p85 subunit of phosphatidylinositol-3 (PI3)-kinase (about 2% of the Caucasian population) have lower glucose tolerance, glucose effectiveness. A further Asp to Tyr polymorphism has been identified at codon 905 of the gene encoding the regulatory subunit of glycogen-associated protein phosphatase-1 (PP1G). Individuals who are heterozygous for this polymorphism constitute 18% of the Caucasian population and appear to exhibit both tissue-specific and pathway-specific insulin resistance. It is likely that inherited insulin resistance will eventually prove to be related to subtle mutations in many such genes of the insulin signalling network and the numerous genetic components controlling energy metabolism.

Animals↗
PubMed2001

Evolution of genome-phenome diversity under environmental stress.

The genomic era revolutionized evolutionary biology. The enigma of genotypic-phenotypic diversity and biodiversity evolution of genes, genomes, phenomes, and biomes, reviewed here, was central in the research program of the Institute of Evolution, University of Haifa, since 1975. We explored the following questions. (i) How much of the genomic and phenomic diversity in nature is adaptive and processed by natural selection? (ii) What is the origin and evolution of adaptation and speciation processes under spatiotemporal variables and stressful macrogeographic and microgeographic environments? We advanced ecological genetics into ecological genomics and analyzed globally ecological, demographic, and life history variables in 1,200 diverse species across life, thousands of populations, and tens of thousands of individuals tested mostly for allozyme and partly for DNA diversity. Likewise, we tested thermal, chemical, climatic, and biotic stresses in several model organisms. Recently, we introduced genetic maps and quantitative trait loci to elucidate the genetic basis of adaptation and speciation. The genome-phenome holistic model was deciphered by the global regressive, progressive, and convergent evolution of subterranean mammals. Our results indicate abundant genotypic and phenotypic diversity in nature. The organization and evolution of molecular and organismal diversity in nature at global, regional, and local scales are nonrandom and structured; display regularities across life; and are positively correlated with, and partly predictable by, abiotic and biotic environmental heterogeneity and stress. Biodiversity evolution, even in small isolated populations, is primarily driven by natural selection, including diversifying, balancing, cyclical, and purifying selective regimes, interacting with, but ultimately overriding, the effects of mutation, migration, and stochasticity.

Animals↗
PubMed1989

I/Lyn mouse phosphorylase kinase deficiency: mutation disrupts expression of the alpha/alpha'-subunit mRNAs.

A cDNA encoding the alpha subunit of mouse skeletal muscle phosphorylase kinase was used to compare the expression of alpha mRNAs in normal and phosphorylase kinase-deficient tissues of the I/Lyn mouse. The results demonstrate that two different molecular weight species of poly(A)+ RNA in normal mouse heart and skeletal muscle hybridize to the alpha cDNA. These two mRNAs direct the synthesis of alpha protein and its isoform alpha' in a cell-free translation system. Thus, alpha and alpha' are encoded by two distinct mRNAs. The abundance of both of these mRNAs is reduced dramatically in the phosphorylase kinase-deficient skeletal muscle and heart tissues from the I/Lyn mouse strain. This result indicates that a mechanism common to both alpha and alpha' expression is disrupted by the I/Lyn mutation. The I/Lyn deficiency is inherited as an X chromosome trait. By Southern mapping of Chinese hamster-mouse cell hybrids the alpha gene was localized to the mouse X chromosome, supporting the possibility that the I/Lyn mutation is in the alpha gene. These results are discussed in terms of a cis or trans mutation influencing the expression of either a single alpha/alpha' gene or two genes encoding alpha and alpha'.

Amino Acid Sequence↗
PubMed2004

Genomic organisation of the chicken ghrelin gene and its single nucleotide polymorphisms detected by denaturing high-performance liquid chromatography.

(1) Ghrelin is a novel endogenous ligand for the growth hormone secretagogue receptor (GHS-R) and is expressed primarily in the stomach and hypothalamus with the probable function of stimulating GH secretion and food intake both in mammals and poultry. The complete sequences of ghrelin gene have been reported in humans and mice; however, that of chickens remains unclear. (2) Here, we report the complete sequence of chicken ghrelin gene (submitted to Genbank; accession number AY303688), which consists of 5 exons and 4 introns. As in mice, the first exon of chicken ghrelin gene does not encode any amino acid. (3) Scanning point mutations with denaturing high-performance liquid chromatography (DHPLC) using WAVE DNA Fragment Analysis Systems and confirmed with direct sequencing for polymerase chain reaction (PCR) products, we analysed the single nucleotide polymorphisms (SNPs) in the entire gene of chicken ghrelin. (4) Results showed that there were 19 SNPs in chicken ghrelin gene, and most of these SNPs were scattered in the 4 introns. In these SNPs, one mutation in exon 5 (A2355G) led to the change of amino acid from glutamine to arginine (Gln 113 Arg): as a result a different ghrelin precursor instead of a mature peptide was produced. In addition, one SNP in 5'UTR (C223G) determined the presence or absence of a potential binding site of transcription factor serum response factor (SRF), which might affect the expression of chicken ghrelin gene. Some of the SNPs detected in the present study could be used in quantitative trait loci (QTL) mapping for growth characters in chickens. (5) Because one SNP is located in a polymorphic site of restriction enzyme PagI of intron 4, it was possible to design a PCR-RFLP procedure and analyse the diversity of 10 chicken populations. Results showed the allelic frequencies of C2100T differ among these breeds, however, no significant difference was observed between imported breeds and Chinese native ones, nor between egg layers and meat type chickens. A chi-square test showed that 4 chicken populations of Beijing Fat, Xinghua, Recessive White and Silky followed the Hardy-Weinberg equilibrium.

Amino Acid Sequence↗
PubMed2003

Harvesting the genomic promise: recombineering sequences for phenotypes.

The past decade has witnessed the construction of linkage and physical maps defining quantitative trait loci (QTL) in various domesticated species. Targeted chromosomal regions are being further characterized through the construction of bacterial artificial chromosome (BAC) contigs in order to isolate and characterize genes contributing towards phenotypic variation. Whole-genome BAC contigs are also being constructed that will serve as the tiling path for genomic sequencing. Harvesting this genetic information for biological gain requires either genetic selection or the production of genetically modified animals. This later approach when coupled with nuclear transfer technology (NT) provides "clones" of genetically modified animals. However, to date, the production of genetically modified animals has been limited to either microinjection of small gene constructs into embryos with random insertion or complex gene constructs designed to knock-out targeted gene expression. Neither of these approaches provides for introducing directed genetic manipulation allowing for allelic substitution [knock-in], subsequent analyses of gene expression, and cloning. An alternative approach utilizing genomic sequence information and recombineering to direct gene targeting of specific porcine BACs is presented here.

Animals↗
PubMed2000

Detection of chromosomal aberrations by a whole-genome microsatellite screen.

Chromosomal aberrations are a common cause of multiple anomaly syndromes that include developmental and growth retardation. Current microscopic techniques are useful for the detection of such aberrations but have a limit of resolution that is above the threshold for phenotypic effect. We hypothesized that a genomewide microsatellite screen could detect chromosomal aberrations that were not detected by standard cytogenetic techniques in a portion of these individuals. To test this hypothesis, we performed a genomewide microsatellite screen of patients, by use of a currently available genetic-marker panel that was originally designed for meiotic mapping of Mendelian traits. We genotyped approximately 400 markers on 17 pairs of parents and their children who had normal karyotypes. By using this approach, we detected and confirmed two cases of segmental aneusomy among 11 children with multiple congenital anomalies. These data demonstrate that a genomewide microsatellite scan can be used to detect chromosomal aberrations that are not detected by microscopic techniques.

Abnormalities, Multiple↗
PubMed2002

Past, present and future strategies to study the genetics of body weight regulation.

Genetic advances have made remarkable progress towards our understanding of body weight regulation. Much of our current knowledge has come from the cloning and characterisation of the genes responsible for obesity syndromes in the mouse, and the identification of homologous mutations causing rare forms of obesity in humans. Gene targeting experiments in mice have been instrumental in confirming the importance of many genes in the aetiology of obesity, and the existence of a fundamental physiological pathway that controls energy balance is becoming clear. The genetic determinants that underlie common forms of human obesity are largely polygenic, with most genes producing small effects. Thus, elucidating the many genetic determinants of obesity is a current challenge for modern geneticists. Despite the inherent difficulties, progress has been made through linkage/association studies and a genetic map of quantitative trait loci for human obesity is beginning to emerge. Obesity research is now very much in a transition period. Not so long ago, access to high throughput screening, as well as microarray and proteomic techniques, was prohibitively expensive and available only to the few. In recent years, these technologies have become more accessible to the larger scientific community and, in this paper, we will discuss how such technological advances are likely to drive the next wave of progress in obesity research. For example, large-scale mutagenesis screens in rodents coupled with high throughput screening are likely to emerge as important technologies for identifying genes previously unexpected to be involved in body weight regulation. Furthermore, applications of microarray and proteomic techniques will further refine our understanding of currently known peptides as well as identify novel pathways and molecules which are involved in energy homeostasis.

Agouti Signaling Protein↗
PubMed1995

Localisation of a gene for chondrocalcinosis to chromosome 5p.

Chondrocalcinosis is a common disorder which may associate with acute and chronic arthritis. A familial form, inherited as an autosomal dominant trait, has been mapped in a large family in which affected members also suffer recurrent fits in childhood. The gene which causes this disease shows linkage with several polymorphic markers on chromosome 5p with a maximum multipoint lod score of 4.6 between D5S810 and D5S416. Mapping a locus for chondrocalcinosis will allow the heterogeneity of the disorder to be assessed and may also be relevant to understanding the aetiology of osteoarthritis with which it commonly associates.

Child↗
PubMedDate not supplied

Mapping of a QTL for serum HDL cholesterol in the rabbit using AFLP technology.

The amplified fragment length polymorphism (AFLP) technique is a DNA technology that generates the so-called AFLP markers. These markers are genomic restriction fragments detected after two rounds of polymerase chain reaction (PCR) without prior knowledge of nucleotide sequence. Here we describe the first application of the AFLP technique in the rabbit. We have tested two primer combinations. The results obtained with the DNA from rabbits of different breeds justify the conclusion that AFLP analysis is an effective tool for genetic studies in the rabbit. In addition, we contribute to the linkage map of the rabbit by localizing two AFLP markers on rabbit linkage group VI (LG VI). For this purpose the progeny of a IIIVO/JU x [IIIVO/JU x AX/JU]F(1) backcross were genotyped for 12 AFLP markers and 3 LG VI classical markers [one coat color marker (e) and two biochemical markers (Es-1 and Est-2)]. AX/JU is a dietary cholesterol-susceptible (hyperresponding) inbred strain and IIIVO/JU is a dietary cholesterol resistant (hyporesponding) inbred strain. Moreover, it is possible to evoke dietary cholesterol-induced aorta atherosclerosis in a relatively short time period in AX/JU rabbits, in contrast to IIIVO/JU rabbits. A significant cosegregation was found between basal serum HDL cholesterol level (i.e., the level on a low-cholesterol, control diet) and an AFLP marker on LG VI. It is concluded that one or more genes of LG VI are regulating the basal serum HDL cholesterol level in rabbits. Thus the present study with rabbits clearly illustrates the value of AFLP markers for the construction of linkage maps and mapping of quantitative trait loci (QTL).

Animals↗
PubMed2003

A major gene locus links early onset albuminuria with renal interstitial fibrosis in the MWF rat with polygenetic albuminuria.

The development of renal interstitial fibrosis (RIF) represents an important step in the progression of chronic proteinuric nephropathies. The Munich Wistar Frömter (MWF) rat represents a valuable model to study the progression in proteinuric renal disease. MWF animals demonstrate a significant increase of urinary albumin excretion (UAE) and RIF compared with the spontaneously hypertensive rat (SHR) with low UAE. The aim of this study was to analyze the genetic basis and the relation between UAE and RIF by genetic linkage and quantitative trait loci (QTL) mapping analysis. The authors generated a backcross population between MWF and SHR including 215 male animals. UAE was determined in young backcross animals at 8 wk, and at 14 and 24 wk of age, respectively. RIF was evaluated by Sirius red staining of kidney sections and quantified by computer-assisted image analysis at 24 wk. Total genome scan analysis identified in total eight QTL linked to UAE and a major locus on chromosome 6. At this locus, homozygosity for the MWF allele exhibited a strong effect on UAE levels (threefold elevation) and displayed significant linkage already at 8 wk (logarithm of odds [LOD] = 4.3) with increasing significance at 14 and 24 wk (LOD = 7.8 and 10.1, respectively). In addition, this was the only QTL that was linked to the amount of RIF (P = 0.0009, LOD = 2.4). These data establish a genetic link between early onset albuminuria and progression of RIF at the QTL on RNO6. This study demonstrates the power of genetic linkage analysis for the dissection of physiologic pathways involved in renal disease progression.

Albuminuria↗
PubMed2025

CSF proteogenomics implicates novel proteins and humoral immunity in Alzheimer's disease risk.

We profiled 2,961 cerebrospinal fluid (CSF) proteins in 1,005 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 1,066 proteins not measured in prior studies, using mass spectrometry (MS). We mapped protein quantitative trait loci (pQTLs) in CSF, compared them with brain and plasma pQTLs, and integrated them with Alzheimer's disease (AD) genome-wide association study (GWAS) data. We identified 1,417 index cis pQTLs for 654 unique genes and 130 index trans pQTLs for 94 unique genes. Cross-tissue and cross-proteomic-platform comparisons show broad consistency between MS-based CSF pQTLs and MS-based brain pQTLs as well as affinity-based CSF and plasma pQTLs. Lastly, through integrating CSF pQTLs with the largest AD GWAS, we identified 24 candidate AD causal proteins in CSF, including 10 novel and 14 previously identified in either brain, CSF, or plasma using similar approaches. These CSF AD candidate causal proteins are involved in immune response - notably humoral immunity (3 of 24) - that expands the role of the immune system in AD beyond innate immunity, as well as lysosomal function and neurovascular growth and remodeling. Together, our findings provide novel insights into AD biology and new targets for biomarker and therapeutic development.

Journal Article↗
PubMed2025

simPIC:flexible simulation of paired-insertion counts for single-cell ATAC sequencing data.

Single-cell Assay for Transposase Accessible Chromatin (scATAC-seq) is increasingly used at population scale to study how genetic variation shapes chromatin accessibility across diverse cell types. This widespread adoption of the assay has created a need for computational methods that can handle complex biological and technical variation. Yet method development is limited by the lack of flexible simulation tools with known ground truth. Here, we present simPIC, a simulation framework for generating realistic single-cell ATAC-seq data across individuals and cell types. simPIC supports both population-scale and single-individual simulations, with the ability to model cell groups, batch effects, and genotype-dependent variation in accessibility. These features enable realistic benchmarking for tasks such as chromatin accessibility quantitative trait locus (caQTL) mapping. simPIC generates data that closely match real datasets and better captures inter-individual and experimental variation compared to existing tools.

simulation↗
PubMed1997

A chromosome-specific microdissected library increases marker density on bovine chromosome 1.

Genetic resolution of bovine chromosome 1 (BTA1) linkage group was significantly increased by screening for microsatellite clones a microdissected library constructed from a bovine cell line carrying a t(1;29) translocation. Eighty-five percent of the microsatellites (ms) (46/54) identified were informative in the USDA/MARC mapping population, and 96% of these ms (44/46) linked to BTA1 (LOD > 3.0). When merged with 40 existing BTA1 markers the genetic map spanned 153.8 cM (sex-averaged interval, 1.9 cM). The fourfold improvement in marker density of BTA1 provides a genetic map that enhances mapping of quantitative trait loci and implementation of marker assisted selection.

Animals↗
PubMed2004

Multiple loci are linked with anti-red blood cell antibody production in NZB mice -- comparison with other phenotypes implies complex modes of action.

The New Zealand Black (NZB) mouse strain is a model of autoimmune haemolytic anaemia (AHA) and systemic lupus erythematosus (SLE), characterized by the production of anti-red blood cell (RBC) antibodies and anti-nuclear antibodies (ANA), respectively. A linkage analysis was carried out in an (NZB x BALB/c) F(2) cross in order to identify loci involved in the production of both anti-RBC IgM and IgG antibodies. These regions of linkage were compared with linkage data to ANA from the same cohort and other linkage analyses involving New Zealand mice. Four previously described NZB loci linked to anti-RBC antibodies were confirmed, and eight novel loci linked to this trait were also mapped: five of which were of NZB origin, and three derived from the non-autoimmune BALB/c background. A comparison between loci linked with anti-RBC antibodies and ANA demonstrated many that co-localize, suggesting the presence of genes that result in the general breaking of tolerance to self-antigen. Furthermore, the observation that some loci were associated only with the anti-RBC response suggests an antigen specific mechanism in addition to a general breaking of tolerance. A locus linked with anti-RBC antibodies and ANA on distal chromosome 7 in this cohort is orthologous to one on the q arm of human chromosome 11, a region linked to AHA and ANA in human SLE.

Anemia, Hemolytic, Autoimmune↗