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PubMed2004

[Identification and analysis of a novel microsatellite marker flanking porcine myostatin gene (MSTN)].

In animal breeding, microsatellite marker plays an important role in constructing genetic maps, QTL mapping and function analysis of structural genes. Myostatin, also known as GDF8, is a negative regulator of skeletal muscle mass and, in swine, it is evidenced to be related to birth weight and average daily gain from 60 kg to 100 kg of body weight. In present study, by subcloning and sequencing,we identified a novel microsatellite marker which is useful for fine QTL mapping for meat traits. A BAC clone containing porcine MSTN was extracted and digested with EcoR I to recover the fragment of > 4 kb for subcloning in pGEM-3zf (+). Sequencing and alignment results showed that this subcloned fragment was not from porcine MSTN, but included a tandem repeat of (TG) 13, which is a novel microsatellite marker (GenBank accession number: AF454400) flanking MSTN. To exclude its vector origin we designed specific primers flanking this marker and successfully amplified this fragment from porcine genome. Through a pedigree analysis of a double-muscled Yorshire strain, we found that it is inherited in a co-dominant manner. We also checked the gene frequencies of this locus in 381 unrelated individuals of 7 pig breeds, namely Laiwu,Landrace, Yorkshire,Duroc, Peterian, Min and Erhualian. Only two alleles were detected, the repeating number of which are 13 (allele A) and 19 (allele B) respectively, which indicated that it is a low poly morphic microsatellite marker. In addition, the frequencies of the two alleles are different between the two types of pig breeds, while allele A is dominant in Chinese local breeds, allele B is dominant in imported breeds. Alignment with AY208121 indicate that this locus is located 42 kb downstream of porcine MSTN. We speculate that this microsatellite DNA is an important marker both in fine QTL mapping for meat traits and in the expression study of porcine MSTN.

Animals↗
PubMed2006

Systematic interpretation of microarray data using experiment annotations.

BACKGROUND: Up to now, microarray data are mostly assessed in context with only one or few parameters characterizing the experimental conditions under study. More explicit experiment annotations, however, are highly useful for interpreting microarray data, when available in a statistically accessible format. RESULTS: We provide means to preprocess these additional data, and to extract relevant traits corresponding to the transcription patterns under study. We found correspondence analysis particularly well-suited for mapping such extracted traits. It visualizes associations both among and between the traits, the hereby annotated experiments, and the genes, revealing how they are all interrelated. Here, we apply our methods to the systematic interpretation of radioactive (single channel) and two-channel data, stemming from model organisms such as yeast and drosophila up to complex human cancer samples. Inclusion of technical parameters allows for identification of artifacts and flaws in experimental design. CONCLUSION: Biological and clinical traits can act as landmarks in transcription space, systematically mapping the variance of large datasets from the predominant changes down toward intricate details.

Cluster Analysis↗
PubMed2005

Cloning, mapping and association study with carcass traits of the porcine SDHD gene.

A 1320-bp cDNA containing the full coding region of the porcine succinate dehydrogenase complex, subunit D (SDHD) gene was obtained by random sequencing of clones from a Chinese Tongcheng pig 55-day fetal longissimus dorsi muscle cDNA library. Analysis of the SDHD gene across the INRA-University of Minnesota porcine radiation hybrid panel indicated close linkage with microsatellite marker SW2401, located on SSC9p21. The open reading frame of this cDNA covers 480 bp and encodes 159 amino acids. The deduced porcine amino acid sequence showed greater similarity with human and bovine protein sequences than with those from mouse and rat. The BLAST analysis of the porcine SDHD to NCBI identified Unigene Cluster Ssc.2586. Possible single nucleotide polymorphisms (SNP) were identified by alignment of expressed sequence tags in the cluster. The polymerase chain reaction (PCR) single strand conformation polymorphism, sequencing, and PCR restriction fragment length polymorphism were used to confirm and detect a synonymous polymorphic MboI site within the open-reading frame. Allele frequencies of this SNP were investigated in two commercial and five Chinese local pig breeds. These five Chinese breeds had very high frequencies for one allele, whereas frequencies of both alleles were intermediate in Large White and Duroc. An association analysis suggested that different SDHD genotypes have significant differences in loin-muscle area (P < 0.01).

Animals↗
PubMed2000

Genetically defined risk of salt sensitivity in an intercross of Brown Norway and Dahl S rats.

A genetic segregation analysis was performed to identify genes that cosegregate with arterial blood pressure traits reflective of salt sensitivity. A population of 113 F2 male rats was derived from an intercross of inbred SS/JrHsd/Mcw (Dahl salt-sensitive) and BN/SsN/Mcw (Brown Norway) rats. Rats were maintained on an 8% salt diet from the age of 9 to 13 wk, and arterial pressure was measured for 3 h daily during the 4th wk of high salt intake in unanesthetized rats using implanted arterial catheters. At the end of the 3rd day of high-salt pressure recordings, the arterial pressure response to salt depletion was determined 1.5 days following treatment with Lasix and a low-sodium (0. 4%) diet. A genome-wide scan using 265 polymorphic simple sequence length polymorphism (SSLP) markers found that seven arterial pressure phenotypes determined at different times and circumstances, and representing two distinct indexes of salt sensitivity, mapped to the same region of rat chromosome 18. The trait of salt sensitivity was strongly influenced by the presence of SS alleles in this region of chromosome 18, and those rats which were homozygote SS/SS exhibited a significantly greater reduction of mean arterial pressure following sodium depletion (29 +/- 2 mmHg) than homozygote BN/BN (17 +/- 3 mmHg) or heterozygotic (22 +/- 2 mmHg) rats. This region of rat chromosome 18 corresponds to the long arm of human chromosome 5 and a region of human chromosome 18 that has been linked to hypertension in humans. Given the unlikely chance of these different blood pressure traits mapping to the same region, we believe these data provide evidence that this region of rat chromosome 18 plays an important role in salt-induced hypertension.

Alleles↗
PubMed2001

Analysis of the sheep genome.

The identification of genes controlling several traits of interest in sheep has been accomplished by positional candidate cloning. In these studies, the trait is first mapped to a specific chromosomal region by linkage analysis, which requires families that are segregating for the trait and for polymorphic markers. Microsatellite markers are usually used for these analyses because of their extensive genetic variability. Once the location of a trait is determined by linkage to the markers, possible candidate genes controlling the trait can be inferred because of their proximity to linked markers. It is not necessary to map all possible genes in sheep for this strategy to be effective. Rather, a subset of genes that are mapped in humans and mice have also been mapped in sheep; these genes serve as "anchors" across the comparative maps of the different species. Further study of these positional candidates has revealed naturally occurring mutations that produce phenotypes that are unique to sheep. Thus the genetic analysis of sheep traits advances knowledge not only in this species but provides critical information for understanding biological pathways in mammalian species.

Animals↗
PubMed2004

TropGENE-DB, a multi-tropical crop information system.

TropGENE-DB, is a crop information system created to store genetic, molecular and phenotypic data of the numerous yet poorly documented tropical crop species. The most common data stored in TropGENE-DB are information on genetic resources (agro-morphological data, parentages, allelic diversity), molecular markers, genetic maps, results of quantitative trait loci analyses, data from physical mapping, sequences, genes, as well as the corresponding references. TropGENE-DB is organized on a crop basis with currently three running modules (sugarcane, cocoa and banana), with plans to create additional modules for rice, cotton, oil palm, coconut, rubber tree, pineapple, taro, yam and sorghum. The TropGENE-DB information system is accessible for consultation via the internet at http://tropgenedb.cirad.fr. Specific web consultation interfaces have been designed to allow quick consultations as well as complex queries.

Computational Biology↗
PubMed2006

QTL mapping for low-dose ethanol activation in the LXS recombinant inbred strains.

BACKGROUND: Most mouse quantitative trait loci (QTLs) for behavioral traits have been mapped using populations of mice derived from C57BL/6J (B6) and DBA/2J (D2). It is also important to identify QTLs for behavior in populations derived from other progenitors. We report results from QTL mapping for low-dose (ethanol) locomotor activation (LDA) using the recently developed LXS recombinant inbred (RI) strains, derived from Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS) progenitors. The LXS RI panel has additional genetic variation, and greater power due to a larger number of strains, compared with other RI panels and strain crosses. METHODS: Mice were tested using a 3-day protocol in which activity levels were monitored for 15 minutes each day. On day 1, baseline activity was recorded; on day 2, mice were injected with saline before testing; and on day 3, mice were injected with 1.8 g/kg ethanol and tested. RESULTS: Several suggestive QTLs were found, on chromosomes 2, 3, 4, 7, 8, 12, and 13; 3 of these QTLs were sex-specific. CONCLUSIONS: Two apparently novel LDA QTLs were identified, on chromosomes 4 and 8. The other QTLs appear to replicate previously identified LDA QTLs. These replicated QTLs will be pursued in subsequent studies designed to identify candidate genes.

Animals↗
PubMed2004

Integration of the rat recombination and EST maps in the rat genomic sequence and comparative mapping analysis with the mouse genome.

Inbred strains of the laboratory rat are widely used for identifying genetic regions involved in the control of complex quantitative phenotypes of biomedical importance. The draft genomic sequence of the rat now provides essential information for annotating rat quantitative trait locus (QTL) maps. Following the survey of unique rat microsatellite (11,585 including 1648 new markers) and EST (10,067) markers currently available, we have incorporated a selection of 7952 rat EST sequences in an improved version of the integrated linkage-radiation hybrid map of the rat containing 2058 microsatellite markers which provided over 10,000 potential anchor points between rat QTL and the genomic sequence of the rat. A total of 996 genetic positions were resolved (avg. spacing 1.77 cM) in a single large intercross and anchored in the rat genomic sequence (avg. spacing 1.62 Mb). Comparative genome maps between rat and mouse were constructed by successful computational alignment of 6108 mapped rat ESTs in the mouse genome. The integration of rat linkage maps in the draft genomic sequence of the rat and that of other species represents an essential step for translating rat QTL intervals into human chromosomal targets.

Animals↗
PubMed2002

Mapping of genetic factors influencing the weight of cystic fibrosis knockout mice.

One of the poorly understood clinical manifestations of cystic fibrosis (CF) is low body weight. Mice in which the CF causative gene, cystic fibrosis transmembrane conductance regulator (Cftr), has been knocked out reflect this as they are smaller than age-matched littermates. The variable weight of F2 Cftr -/- (CF) mice derived from a cross between congenic C57BL/6J and BALB/cJ Cftr heterozygotic mice permits the mapping of modifiers of this cystic fibrosis phenotype. In this report, quantitative trait loci (QTL) mapping was used to identify the chromosomal locations of genes that contribute to the body weight of 12-week-old F2 CF mice. Five loci of CF body weight were detected with four of the five acting in a sex-specific manner. Significant linkage of the phenotype to a region of Chromosome (Chr) 13 from D13Mit179 to D13Mit254 (LOD = 4.2) was established in female mice; and suggestive loci on Chrs 7 and 10 were identified. The weights of F2 male CF mice were suggestively linked to regions of Chrs 1 and 6, and to the same locus on Chr 7 as in female mice. The suggestive loci did not influence the weight of the limited set of control mice and thus are presumed to be CF specific in their effects. Further study of these putative CF body weight modifiers may provide insight on the pathogenesis of cystic fibrosis.

Animals↗
PubMed2006

A novel locus on the X chromosome regulates post-maturity bone density changes in mice.

Two mouse strains, AKR/J and SAMP6, were assessed longitudinally for bone mineral density of the spine. They displayed very different time courses of bone accrual, with the SAMP6 strain reaching a plateau for vertebral BMD at 3 months, whereas AKR/J mice continued to increase spine BMD for at least 8 months. Among 253 F(2) progeny of an AKR/JxSAMP6 cross, at 4 months of age, the BMD variance was 5-6% of the mean, vs. 15% for weight. Variance increased with age for every parameter measured, and was generally higher among males. The ratio of 6-month/4-month spine BMDs, termed DeltasBMD, had a normal distribution with 5.7% variance, and was largely independent of spine BMD (R=-0.23) or body weight (R=-0.12) at maturity. Heritability of the DeltasBMD trait was calculated at 0.59. Genetic mapping identified two significant loci, both distinct from those observed for BMD at maturity--implying that different genes regulate skeletal growth vs. remodeling. A locus on the X chromosome, replicated in two mouse F(2) populations (P<10(-4) for combined discovery and confirmation), affects age-dependent BMD change for both spine and the full skeleton. Its position agrees with a very narrow region identified by association mapping for effects on lumbar bone density in postmenopausal women [Parsons CA, Mroczkowski HJ, McGuigan FE, Albagha OM, Manolagas S, Reid DM, et al. Interspecies synteny mapping identifies a quantitative trait locus for bone mineral density on human chromosome Xp22. Hum Mol Genet 2005;14:3141-8]. A second locus, on chromosome 7, was observed in only one cross. Single-nucleotide polymorphisms (SNPs) are highly clustered near these loci, distinguishing the parental strains over only limited spans.

Absorptiometry, Photon↗
PubMed2001

Interval mapping of carcass and meat quality traits in a divergent swine cross.

An autosomal scan of the swine genome with 119 polymorphic microsatellite (ms) markers and data from 116 F2 barrows of the University of Illinois Meishan x Yorkshire Swine Resource Families identified genomic regions with effects on variance in carcass composition and meat quality at nominal significance (p-value <0.05). Marker intervals on chromosomes 1, 6, 7, 8 and 12 (SSC1, SSC6, SSC7, SSC8, SSC12) with phenotypic effects on carcass length, 10th rib backfat thickness, average backfat thickness, leaf fat, loin eye area and intramuscular fat content confirm QTL effects identified previously based on genome wide significance (p-value <0.05). Several marker intervals included nominally significant (p-value <0.05) dominance effects on leaf fat, 10th rib backfat thickness, loin eye area, muscle pH and intramuscular fat content.

Adipose Tissue↗
PubMed2001

Allelic association and disease mapping.

The application of allelic association to map genes for complex traits, particularly using high-density maps of single nucleotide polymorphisms in candidate regions, is an area of very active research. Here we present some aspects of the methodology and applications to both major gene mapping, which illustrates the effectiveness of the method, and oligogenes, where methods are still in flux and for which there have been relatively few successes to date. Several important considerations emerge, including the selection of the optimal metric for measuring association and the importance of modelling the decline in association with distance given the variability in association in a candidate region. The Malecot model of association with distance is shown to have a resolution of greater than 50 kilobases but the available evidence suggests that considerably higher resolution might be achieved with dense single nucleotide polymorphism (SNP) maps.

Alleles↗
PubMed2003

Quantitative trait loci analysis of water and anion contents in interaction with nitrogen availability in Arabidopsis thaliana.

In plants, water and anion parameters are linked, for example through the integration of nutritional signaling and the response to diverse stress. In this work, Arabidopsis thaliana is used as a model system to dissect the genetic variation of these parameters by quantitative trait loci (QTL) mapping in the 415 recombinant inbred lines of the Bay-0 x Shahdara population. Water, nitrate, chloride, and phosphate contents were measured at the vegetative stage in the shoots of plants grown in controlled conditions. Two contrasting nitrogen (N) conditions were studied, one leading to the complete depletion of the nitrate pool in the plants. Most of the observed genetic variation was identified as QTL, with medium but also large phenotypic contributions. QTL colocalization provides a genetic basis for the correlation between water and nitrate contents in nonlimiting N conditions and water and chloride contents in limiting N conditions. The 34 new QTL described here represent at least 19 loci polymorphic between Bay-0 and Shahdara; some may correspond to known genes from water/anion transport systems, while others clearly identify new genes controlling or interacting with water/anion absorption and accumulation. Interestingly, flowering-time genes probably play a role in the regulation of water content in our conditions.

Anions↗
PubMed1999

Mapping of a blood pressure quantitative trait locus to chromosome 15q in a Chinese population.

Blood pressure is a complex trait of pivotal biological importance, in which 20-50% of interindividual variation is genetically determined. Whereas genes have been identified in several rare Mendelian forms of hypertension, little progress has been made in understanding the genetics of blood pressure variation in the general population. Recently, we screened the human genome using rural Chinese sibling pairs with extreme blood pressure and identified suggestive linkage for two chromosomal regions. By refining the trait definition and genotyping additional markers, we detected significant linkage (maximum lod score = 3.77) near D15S203 in lower extreme diastolic blood pressure sibling pairs. Using a second independent data set from the same geographical area, we marginally replicated ( P = 0.05) this result, suggesting that this locus is very likely to be involved in the regulation of diastolic blood pressure.

Adult↗
PubMed2007

Comparative genetics of potential prezygotic and postzygotic isolating barriers in a Lycopersicon species cross.

I compare the genetic basis of quantitative traits that potentially contribute to pre- and postzygotic isolation between the plant species Solanum lycopersicum (formerly Lycopersicon esculentum) and Solanum habrochaites (formerly Lycopersicon hirsutum), using quantitative trait loci (QTL) mapping in a set of near-isogenic lines. Putative prezygotic isolating traits include flower size, flower shape, stigma exertion, and inflorescence length, that can influence pollinator preferences and/or selfing rates, and therefore gene flow between divergent types. Postzygotic isolating traits are hybrid pollen and seed sterility. Three substantive results emerge from these analyses. First, the genetic basis of floral differentiation appears to be somewhat less complex than the genetic basis of postzygotic hybrid sterility, although these differences are very modest. Second, there is little evidence that traits for floral differentiation are causally or mechanistically associated with hybrid sterility traits in this species cross. Third, there is little evidence that hybrid sterility QTL are more frequently associated with chromosomal centromeric regions, in comparison to floral trait QTL, a prediction of centromeric drive models of hybrid sterility. Although genome-wide associations are not evident in this analysis, several individual chromosomal regions that contain clusters of QTL for both floral and sterility traits, or that indicate hybrid sterility effects at centromere locations, warrant further fine-scale investigation.

Centromere↗
PubMed2006

Haplotype variation in structure and expression of a gene cluster associated with a quantitative trait locus for improved yield in rice.

By constructing nearly isogenic lines (NILs) that differ only at a single quantitative trait locus (QTL), we fine-mapped the yield-improving QTL qGY2-1 to a 102.9-kb region on rice chromosome 2. Comparison analysis of the genomic sequences in the mapped QTL region between the donor (Dongxiang wild rice, Oryza rufipogon Griff.) and recurrent (Guichao2, Oryza sativa ssp. indica) parents used for the development of NILs identified the haplotypes of a leucine-rich repeat receptor kinase gene cluster, which showed extensive allelic variation. The sequences between genes in the cluster had a very high rate of divergence. More importantly, the genes themselves also differed between two haplotypes: Only 92% identity was observed for one allele, and another allele was found to have completely lost its allelic counterpart in Guichao2. The other six shared genes all showed >98% identity, and four of these exhibited obvious regulatory variation. The same haplotype segments also differed in length (43.9-kb in Guichao2 vs. 52.6-kb in Dongxiang wild rice). Such extensive sequence variation was also observed between orthologous regions of indica (cv. 93-11) and japonica (cv. Nipponbare) subspecies of Oryza sativa. Different rates of sequence divergence within the cluster have resulted in haplotype variability in 13 rice accessions. We also detected allelic expression variation in this gene cluster, in which some genes gave unequal expression of alleles in hybrids. These allelic variations in structure and expression suggest that the leucine-rich repeat receptor kinase gene cluster identified in our study should be a particularly good candidate for the source of the yield QTL.

Alleles↗
PubMedDate not supplied

AFLP linkage map of the Japanese quail Coturnix japonica.

The quail is a valuable farm and laboratory animal. Yet molecular information about this species remains scarce. We present here the first genetic linkage map of the Japanese quail. This comprehensive map is based solely on amplified fragment length polymorphism (AFLP) markers. These markers were developed and genotyped in an F2 progeny from a cross between two lines of quail differing in stress reactivity. A total of 432 polymorphic AFLP markers were detected with 24 TaqI/EcoRI primer combinations. On average, 18 markers were produced per primer combination. Two hundred and fifty eight of the polymorphic markers were assigned to 39 autosomal linkage groups plus the ZW sex chromosome linkage groups. The linkage groups range from 2 to 28 markers and from 0.0 to 195.5 cM. The AFLP map covers a total length of 1516 cM, with an average genetic distance between two consecutive markers of 7.6 cM. This AFLP map can be enriched with other marker types, especially mapped chicken genes that will enable to link the maps of both species and make use of the powerful comparative mapping approach. This AFLP map of the Japanese quail already provides an efficient tool for quantitative trait loci (QTL) mapping.

Animals↗