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At least 1,207 records · Page 67Linked to original sources
PubMed2005

The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2.

BACKGROUND: We previously mapped a quantitative trait locus (QTL) for ethanol preference drinking to mouse chromosome 2 (mapped with high confidence, LOD = 15.5, p = 3 x 10(-16)). The specific gene(s) in the QTL interval responsible for phenotypic variation in ethanol preference drinking has not been identified. METHODS: In the current study, we investigated the association of the syntaxin binding protein 1 gene (Stxbp1) with ethanol preference drinking and other ethanol traits using a panel of B6 x D2 (BXD) recombinant inbred (RI) strains derived from the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. Confirmation analyses for ethanol consumption and withdrawal were performed using a large B6D2 F2 cross, short-term selected lines derived from the B6 and D2 progenitor strains, and standard inbred strains. RESULTS: BXD RI strain analysis detected provisional associations between Stxbp1 molecular variants and ethanol consumption, as well as severity of acute ethanol withdrawal, ethanol-conditioned taste aversion, and ethanol-induced hypothermia. Confirmation analyses using three independent genetic models supported the involvement of Stxbp1 in ethanol preference drinking but not in ethanol withdrawal. CONCLUSIONS: Stxbp1 encodes a Sec1/Munc18-type protein essential for vesicular neurotransmitter release. The present study provides supporting evidence for the involvement of Stxbp1 in ethanol preference drinking.

Alcohol Drinking↗
PubMed1998

Mapping genes for psychiatric disorders and behavioral traits.

In the past year, findings from genetic studies in non-human organisms have yielded a number of exciting insights regarding the genetic basis of complex behaviors. Although there were encouraging developments in the genetic study of human behavioral traits, particularly those involved with cognitive function, there was relatively little progress in genetic mapping of the most common psychiatric phenotypes.

Animals↗
PubMed2006

A distant upstream enhancer at the maize domestication gene tb1 has pleiotropic effects on plant and inflorescent architecture.

Although quantitative trait locus (QTL) mapping has been successful in describing the genetic architecture of complex traits, the molecular basis of quantitative variation is less well understood, especially in plants such as maize that have large genome sizes. Regulatory changes at the teosinte branched1 (tb1) gene have been proposed to underlie QTLs of large effect for morphological differences that distinguish maize (Zea mays ssp. mays) from its wild ancestors, the teosintes (Z. mays ssp. parviglumis and mexicana). We used a fine mapping approach to show that intergenic sequences approximately 58-69 kb 5' to the tb1 cDNA confer pleiotropic effects on Z. mays morphology. Moreover, using an allele-specific expression assay, we found that sequences >41 kb upstream of tb1 act in cis to alter tb1 transcription. Our findings show that the large stretches of noncoding DNA that comprise the majority of many plant genomes can be a source of variation affecting gene expression and quantitative phenotypes.

Genes, Plant↗
PubMed2002

Backward Haplotype Transmission Association (BHTA) algorithm - a fast multiple-marker screening method.

The mapping of complex traits is one of the most important and central areas of human genetics today. Recent attention has been focused on genome scans using a large number of marker loci. Because complex traits are typically caused by multiple genes, the common approaches of mapping them by testing markers one after another fail to capture the substantial information of interactions among disease loci. Here we propose a backward haplotype transmission association (BHTA) algorithm to address this problem. The algorithm can administer a screening on any disease model when case-parent trio data are available. It identifies the important subset of an original larger marker set by eliminating the markers of least significance, one at a time, after a complete evaluation of its importance. In contrast with the existing methods, three major advantages emerge from this approach. First, it can be applied flexibly to arbitrary markers, regardless of their locations. Second, it takes into account haplotype information; it is more powerful in detecting the multifactorial traits in the presence of haplotypic association. Finally, the proposed method can potentially prove to be more efficient in future genomewide scans, in terms of greater accuracy of gene detection and substantially reduced number of tests required in scans. We illustrate the performance of the algorithm with several examples, including one real data set with 31 markers for a study on the Gilles de la Tourette syndrome. Detailed theoretical justifications are also included, which explains why the algorithm is likely to select the 'correct' markers.

Algorithms↗
PubMed2006

A statistical model to analyse quantitative trait locus interactions for HIV dynamics from the virus and human genomes.

Viruses can be considered 'parasites' because they cannot survive outside of a host. The progression rate to AIDS caused by human immunodeficiency virus type-1 (HIV-1) is therefore a consequence of HIV-host cell interactions. In this article, we present an innovative statistical model for detecting the effects of genetic interactions on HIV-1 dynamics triggered by different quantitative trait loci (QTL) from the HIV and human genomes. Our model integrates the principles of functional mapping for longitudinal traits and of linkage disequilibrium analysis for high-resolution mapping of QTL within the maximum likelihood context and is implemented with the EM algorithm. We performed Monte Carlo simulation studies to investigate the impacts of different heritability levels and sample sizes on the power to detect interacting QTL. Our model allows for the tests of a number of clinically meaningful hypotheses and provides a powerful tool for unravelling the genetic architecture of HIV-1 dynamics and therefore AIDS progression rate.

Algorithms↗
PubMed2004

Major quantitative trait locus for resting heart rate maps to a region on chromosome 4.

Multiple studies have identified resting heart rate as a risk factor for cardiovascular disease independent of other cardiovascular disease risk factors (such as dyslipidemia and hypertension). Previous studies have examined heart rate in hypertensive individuals, but little is known about the genetic determination of resting heart rate in a normal population. Therefore, our objective was to perform a genome screen on a population containing normotensive and hypertensive individuals. We performed variance decomposition linkage analysis using maximum likelihood methods at approximately 10 cM intervals in 2209 individuals of predominantly North European ancestry. We estimated the heritability of resting heart rate to be 26% and obtained significant evidence of linkage (logarithm of the odds [LOD]=3.9) for resting heart rate on chromosome 4q. This signal is in the same region as a quantitative trait locus (QTL) for long QT syndrome 4 and a QTL for heart rate in rats. Within the 1-LOD unit support interval, there are 2 strong candidates: ankyrin-B and myozenin 2.

Animals↗
PubMed2006

Global eQTL mapping reveals the complex genetic architecture of transcript-level variation in Arabidopsis.

The genetic architecture of transcript-level variation is largely unknown. The genetic determinants of transcript-level variation were characterized in a recombinant inbred line (RIL) population (n = 211) of Arabidopsis thaliana using whole-genome microarray analysis and expression quantitative trait loci (eQTL) mapping of transcript levels as expression traits (e-traits). Genetic control of transcription was highly complex: one-third of the quantitatively controlled transcripts/e-traits were regulated by cis-eQTL, and many trans-eQTL mapped to hotspots that regulated hundreds to thousands of e-traits. Several thousand eQTL of large phenotypic effect were detected, but almost all (93%) of the 36,871 eQTL were associated with small phenotypic effects (R(2) < 0.3). Many transcripts/e-traits were controlled by multiple eQTL with opposite allelic effects and exhibited higher heritability in the RILs than their parents, suggesting nonadditive genetic variation. To our knowledge, this is the first large-scale global eQTL study in a relatively large plant mapping population. It reveals that the genetic control of transcript level is highly variable and multifaceted and that this complexity may be a general characteristic of eukaryotes.

Arabidopsis↗
PubMed2003

Genetic markers and their application in poultry breeding.

The current chicken genetic map contains at least 1,965 loci within 50 linkage groups, and it covers about 4,000 cM. About 235 of these loci have homology with known human or mammalian genes. The remaining loci are anonymous molecular DNA markers, including microsatellites, amplified fragment length polymorphism (AFLP), randomly amplified polymorphic DNA (RAPD), CR1 elements, and others. A third generation genetic map for human uses single nucleotide polymorphisms (SNP), which have allowed the mapping of complex traits by linkage disequilibrium. One advantage of SNP is that they are usually linked to the gene of interest, and association of the SNP with traits of economic importance can be analyzed using candidate gene approaches. With the tremendous advancements in characterizing chicken expressed sequence tags (EST), the identification of genetic polymorphisms such as SNP in chicken genes has become a reality. Our laboratory has undertaken an in silico analysis of the chicken EST at the University of Delaware by using a Phred/Phrap/Polyphred/Consed pipeline to identify candidate chicken SNP. Initial scanning of 23,427 chicken EST identified a total of 1,209 candidate SNP, with at least 182 non-synonymous SNP that result in an amino acid change observed. Validation of these candidate chicken SNP is ongoing. Placement of the SNP on the chicken genetic map will enhance marker density, thus allowing for mapping of complex traits through linkage analysis and linkage disequilibrium. Application of SNP to identify disease resistance genes in chickens is of special interest to our laboratory, especially in regards to Marek's disease and coccidiosis.

Animal Husbandry↗
PubMed1999

Mapping of post-flowering drought resistance traits in grain sorghum: association between QTLs influencing premature senescence and maturity.

The identification of genetic factors underlying the complex responses of plants to drought stress provides a solid basis for improving drought resistance. The staygreen character in sorghum (Sorghum bicolor L. Moench) is a post-flowering drought resistance trait, which makes plants resistant to premature senescence under drought stress during the grainfilling stage. The objective of this study was to identify quantitative trait loci (QTLs) that control premature senescence and maturity traits, and to investigate their association under post-flowering drought stress in grain sorghum. A genetic linkage map was developed using a set of recombinant inbred lines (RILs) obtained from the cross B35 x Tx430, which were scored for 142 restriction fragment length polymorphism (RFLP) markers. The RILs and their parental lines were evaluated for post-flowering drought resistance and maturity in four environments. Simple interval mapping identified seven stay-green QTLs and two maturity QTLs. Three major stay-green QTLs (SGA, SGD and SGG) contributed to 42% of the phenotypic variability (LOD 9.0) and four minor QTLs (SGB, SGI. 1, SGI.2, and SGJ) significantly contributed to an additional 25% of the phenotypic variability in stay-green ratings. One maturity QTL (DFB) alone contributed to 40% of the phenotypic variability (LOD 10.0), while the second QTL (DFG) significantly contributed to an additional 17% of the phenotypic variability (LOD 4.9). Composite interval mapping confirmed the above results with an additional analysis of the QTL x Environment interaction. With heritability estimates of 0.72 for stay-green and 0.90 for maturity, the identified QTLs explained about 90% and 63% of genetic variability for stay-green and maturity traits, respectively. Although stay-green ratings were significantly correlated (r = 0.22, P< or =0.05) with maturity, six of the seven stay-green QTLs were independent of the QTLs influencing maturity. Similarly, one maturity QTL (DFB) was independent of the staygreen QTLs. One stay-green QTL (SGG), however, mapped in the vicinity of a maturity QTL (DFG), and all markers in the vicinity of the independent maturity QTL (DFB) were significantly (P< or =0.1) correlated with stay-green ratings, confounding the phenotyping of stay-green. The molecular genetic analysis of the QTLs influencing stay-green and maturity, together with the association between these two inversely related traits, provides a basis for further study of the underlying physiological mechanisms and demonstrates the possibility of improving drought resistance in plants by pyramiding the favorable QTLs.

Agriculture↗
PubMed2002

Genetics of ethylene biosynthesis and restriction fragment length polymorphisms (RFLPs) of ACC oxidase and synthase genes in melon ( Cucumis melo L.).

We investigated the genetics of ethylene biosynthesis and its linkage to the RFLPs of the ACC oxidase and synthase genes in melon ( Cucumis melo L.). The results suggested that the A(0) and B(0) fragments of RFLP-MEL1 of the ACC oxidase gene were two alleles from a single locus, as were the B and C fragments of RFLP-MEACS1 of the ACC synthase gene. The B(0) allele seemed to be partially dominant over the A(0) allele, whereas B and C alleles appeared to map to quantitative trait loci (QTLs), which most likely contributed to ethylene production. Both RFLPs were linked to ethylene production rates, but they were not linked to each other. The interaction effects of the ACC oxidase and synthase genes on ethylene production were revealed by segregation of RFLP-MEL1 and RFLP-MEACS1. The results of single-copy-reconstruction assays suggested that the ACC oxidase gene is a single copy, whereas the ACC synthase gene is a component of a multigene family in the melon genome. The abscission phenotype appeared to be controlled by an independent locus, with the abscission (full-slip) allele dominant over the non-abscission (not full-slip) allele. These results may facilitate efforts toward mapping the quantitative trait loci (QTLs) of ethylene production. The RFLPs may be used in marker-assisted selection in developing melons with a more-desirable low ethylene production rate for enhancing postharvest storage life.

Journal Article↗
PubMed2003

Linkage analysis for mapping genes of sex-influenced traits.

Statistical methods are developed to estimate gender-specific and gender-average recombination frequencies between a biallelic or multiallelic marker and a sex-influenced gene. Iterative solutions are developed for intercross (or F-2 design). For biallelic markers, two iterative solutions are required, one for coupling and repulsion parental linkage phases and one for mixed parental linkage phases. For multiallelic markers, one set of iterative equations applies to all possible parental linkage phases. The resulting formulae for estimating recombination frequency use the full data set and yield estimates that are exactly the same as the true parameters if the observed and expected phenotypic distributions are equal. When one parent is homozygous for the sex-influenced gene as is expected with the backcross design, simple solutions exist for estimating recombination frequencies. However, offspring of one gender (male or female) do not have linkage information depending on whether the homozygous parent has two male-dominant or male-recessive alleles. Consequently, an F-2 design is more efficient than a backcross design for mapping a sex-influenced gene. Knowing each parental linkage phase is important to apply the methods developed in this article. It is shown that an individual's linkage phase of the sex-influenced locus can be determined based on allele transmission from the parents for all crosses except under the mating between an expressed male and an unexpressed female.

Animals↗
PubMed2006

Design of microarray experiments for genetical genomics studies.

Microarray experiments have been used recently in genetical genomics studies, as an additional tool to understand the genetic mechanisms governing variation in complex traits, such as for estimating heritabilities of mRNA transcript abundances, for mapping expression quantitative trait loci, and for inferring regulatory networks controlling gene expression. Several articles on the design of microarray experiments discuss situations in which treatment effects are assumed fixed and without any structure. In the case of two-color microarray platforms, several authors have studied reference and circular designs. Here, we discuss the optimal design of microarray experiments whose goals refer to specific genetic questions. Some examples are used to illustrate the choice of a design for comparing fixed, structured treatments, such as genotypic groups. Experiments targeting single genes or chromosomic regions (such as with transgene research) or multiple epistatic loci (such as within a selective phenotyping context) are discussed. In addition, microarray experiments in which treatments refer to families or to subjects (within family structures or complex pedigrees) are presented. In these cases treatments are more appropriately considered to be random effects, with specific covariance structures, in which the genetic goals relate to the estimation of genetic variances and the heritability of transcriptional abundances.

Animals↗
PubMed2005

DFNB48, a new nonsyndromic recessive deafness locus, maps to chromosome 15q23-q25.1.

Nonsyndromic deafness locus (DFNB48) segregating as an autosomal recessive trait has been mapped to the long arm of chromosome 15 in bands q23-q25.1 in five large Pakistani families. The deafness phenotype in one of these five families (PKDF245) is linked to D15S1005 with a lod score of 8.6 at theta=0, and there is a critical linkage interval of approximately 7 cM on the Marshfield human genetic map, bounded by microsatellite markers D15S216 (70.73 cM) and D15S1041 (77.69 cM). MYO9A, NR2E3, BBS4, and TMC3 are among the candidate genes in the DFNB48 region. The identification of another novel nonsyndromic recessive deafness locus demonstrates the high degree of locus heterogeneity for hearing impairment, particularly in the Pakistani population.

Chromosome Mapping↗
PubMed2005

Weighting by heritability for detection of quantitative trait loci with microarray estimates of gene expression.

Heritable differences in transcribed RNA levels can be mapped as quantitative trait loci (QTLs). Transcribed RNA levels are often measured by hybridization to microarrays of oligonucleotide probes, in which each transcript is represented by multiple probes. The use of recombinant inbred lines allows an estimate of the heritability of expression measured by individual probes. This heritability varies greatly. We have tested heritability-weighted averages to define expression of a transcript and found that these allow detection of more QTLs than previously described methods.

Animals↗
PubMed2003

Genome-wide scan in a large complex pedigree with predominantly male schizophrenics from the island of Kosrae: evidence for linkage to chromosome 2q.

It is widely accepted that founder populations hold promise for mapping loci for complex traits. However, the outcome of these mapping efforts will most likely depend on the individual demographic characteristics and historical circumstances surrounding the founding of a given genetic isolate. The 'ideal' features of a founder population are currently unknown. The Micronesian islandic population of Kosrae, one of the four islands comprising the Federated States of Micronesia (FSM), was founded by a small number of settlers and went through a secondary genetic 'bottleneck' in the mid-19th century. The potential for reduced etiological (genetic and environmental) heterogeneity, as well as the opportunity to ascertain extended and statistically powerful pedigrees makes the Kosraen population attractive for mapping schizophrenia susceptibility genes. Our exhaustive case ascertainment from this islandic population identified 32 patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder. Three of these were siblings in one nuclear family, and 27 were from a single large and complex schizophrenia kindred that includes a total of 251 individuals. One of the most startling findings in our ascertained sample was the great difference in male and female disease rates. A genome-wide scan provided initial suggestive evidence for linkage to markers on chromosomes 1, 2, 3, 7, 13, 15, 19, and X. Follow-up multipoint analyses gave additional support for a region on 2q37 that includes a schizophrenia locus previously identified in another small genetic isolate, with a well-established recent genealogical history and a small number of founders, located on the eastern border of Finland. In addition to providing further support for a schizophrenia susceptibility locus at 2q37, our results highlight the analytic challenges associated with extremely large and complex pedigrees, as well as the limitations associated with genetic studies of complex traits in small islandic populations.

Adolescent↗
PubMed2025

Saturating the eQTL map in Drosophila: Genome-wide patterns of cis and trans regulation of transcriptional variation in outbred populations.

Most genetic polymorphisms associated with complex traits are found in non-coding regions of the genome. Characterizing their effect presents a formidable challenge, and expression quantitative trait locus (eQTLs) mapping has been a key approach to do so. As comprehensive eQTL maps are available only for a few species, here we developed the Drosophila outbred synthetic population (Dros-OSP) and used it to characterize the landscape of transcriptional regulation in Drosophila melanogaster. We collected head and body transcriptomes and genomes from 1,286 outbred flies and mapped local and distant eQTLs for 98% of the genes. We characterized the network organization of the transcriptome across tissues and described the properties of local and distal eQTLs in terms of genetic diversity, heritability, connectivity, and pleiotropy. These results provide new insights into the genetic basis of transcriptional regulation in the fruit fly and offer a new mapping resource that will expand the possibilities currently available for the Drosophila community.

Animals↗
PubMed1995

Mapping genes for psychiatric disorders and behavioral traits.

In the past year, some of the most exciting findings in the genetic investigation of mammalian behavior have been obtained through mapping and through gene manipulation studies in the mouse system. These include the localization of a gene for circadian periodicity in the mouse, gene knockouts of serotonin receptors, and the development of a transgenic model of Alzheimer's disease. The recent development of genetic maps covering the entire human genome and the implementation of new approaches to genetic analysis may now facilitate elucidation of complex behaviors in humans, particularly psychiatric disorders.

Alleles↗
PubMed2003

Molecular mapping in tropical maize (Zea mays L.) using microsatellite markers. 2. Quantitative trait loci (QTL) for grain yield, plant height, ear height and grain moisture.

A previous genetic map containing 117 microsatellite loci and 400 F(2) plants was used for quantitative trait loci (QTL) mapping in tropical maize. QTL were characterized in a population of 400 F(2:3) lines, derived from selfing the F(2) plants, and were evaluated with two replications in five environments. QTL determinations were made from the mean of these five environments. Grain yield (GY), plant height (PH), ear height (EH) and grain moisture (GM) were measured. Variance components for genotypes (G), environments (E) and GxE interaction were highly significant for all traits. Heritability was 0.69 for GY, 0.66 for PH, 0.67 for EH and 0.23 for GM. Using composite interval mapping (CIM), a total of 13 distinct QTLs were identified: four for GY, four for PH and five for EH. No QTL was detected for GM. The QTL explained 32.73 % of the phenotypic variance of GY, 24.76 % of PH and 20.91 % of EH. The 13 QTLs displayed mostly partial dominance or overdominance gene action and mapped to chromosomes 1, 2, 7, 8 and 9. Most QTL alleles conferring high values for the traits came from line L-14-4B. Mapping analysis identified genomic regions associated with two or more traits in a manner that was consistent with correlation among traits, supporting either pleiotropy or tight linkage among QTL. The low number of QTLs found, can be due to the great variation that exists among tropical environments.

Microsatellite Repeats↗