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QTL Interval (qtl + interval)

Distribution by Scientific Domains

Medical Sciences	66%

Selected Abstracts

Identification of Candidate Genes for Alcohol Preference by Expression Profiling of Congenic Rat Strains

ALCOHOLISM, Issue 7 2007
Lucinda G. Carr
Background: A highly significant quantitative trait locus (QTL) on chromosome 4 that influenced alcohol preference was identified by analyzing crosses between the iP and iNP rats. Congenic strains in which the iP chromosome 4 QTL interval was transferred to the iNP (NP.P) exhibited the expected increase in alcohol consumption compared with the iNP background strain. This study was undertaken to identify genes in the chromosome 4 QTL interval that might contribute to the differences in alcohol consumption between the alcohol-naïve congenic and background strains. Methods: RNA from 5 brain regions from each of 6 NP.P and 6 iNP rats was labeled and analyzed separately on an Affymetrix Rat Genome 230 2.0 microarray to look for both cis -regulated and trans -regulated genes. Expression levels were normalized using robust multi-chip average (RMA). Differential gene expression was validated using quantitative real-time polymerase chain reaction. Five individual brain regions (nucleus accumbens, frontal cortex, amygdala, hippocampus, and striatum) were analyzed to detect differential expression of genes within the introgressed QTL interval, as well as genes outside that region. To increase the power to detect differentially expressed genes, combined analyses (averaging data from the 5 discrete brain regions of each animal) were also carried out. Results: Analyses within individual brain regions that focused on genes within the QTL interval detected differential expression in all 5 brain regions; a total of 35 genes were detected in at least 1 region, ranging from 6 genes in the nucleus accumbens to 22 in the frontal cortex. Analysis of the whole genome detected very few differentially expressed genes outside the QTL. Combined analysis across brain regions was more powerful. Analysis focused on the genes within the QTL interval confirmed 19 of the genes detected in individual regions and detected 15 additional genes. Whole genome analysis detected 1 differentially expressed gene outside the interval. Conclusions: Cis -regulated candidate genes for alcohol consumption were identified using microarray profiling of gene expression differences in congenic animals carrying a QTL for alcohol preference. [source]

A functional genomics approach to evaluate candidate genes located in a QTL interval for milk production traits on BTA6

ANIMAL GENETICS, Issue 4 2009
P. A. Sheehy
Summary The potential genetic and economic advantage of marker-assisted selection for enhanced production in dairy cattle has provided an impetus to conduct numerous genome scans in order to identify associations between DNA markers and future productive potential. One area of focus has been a quantitative trait locus on bovine chromosome 6 (BTA6) found to be associated with milk yield, milk protein and fat percentage, which has been subsequently fine-mapped to six positional candidate genes. Subsequent investigations have yet to resolve which of the potential positional candidate genes is responsible for the observed associations with productive performance. In this study, we analysed candidate gene expression and the effects of gene knockdown on expression of ,- and ,-casein mRNA in a small interfering RNA transfected bovine in vitro mammosphere model. From our expression studies in vivo, we observed that four of the six candidates (ABCG2, SPP1, PKD2 and LAP3) exhibited differential expression in bovine mammary tissue over the lactation cycle, but in vitro functional studies indicate that inhibition of only one gene, SPP1, had a significant impact on milk protein gene expression. These data suggest that the gene product of SPP1 (also known as osteopontin) has a significant role in the modulation of milk protein gene expression. While these findings do not exclude other positional candidates from influencing lactation, they support the hypothesis that the gene product of SPP1 is a significant lactational regulatory molecule. [source]

Refinement of two female fertility QTL using alternative phenotypes in French Holstein dairy cattle

ANIMAL GENETICS, Issue 1 2007
F. Guillaume
Summary Two quantitative trait loci (QTL) affecting female fertility were mapped in French dairy cattle. Phenotypes were non-return rates at 28, 56, 90 and 282 days after insemination. On chromosome 3, a QTL was significant at 1% for non-return rate at 90 days, suggesting that it affects early fertility events. An analysis of SLC35A3, which causes complex vertebral malformation, excluded this gene from the QTL interval. On chromosome 7, a QTL was almost significant (P = 0.05) for non-return rate at 282 days. This QTL was associated with abortion and stillbirth problems. Use of appropriate phenotypes appeared important for fine-mapping QTL associated with fertility. [source]

Genome-wide linkage and QTL mapping in porcine F2 families generated from Pietrain, Meishan and Wild Boar crosses

JOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 6 2003
H. Geldermann
Summary Three informative pig F2 families based on European Wild Boar (W), Meishan (M) and Pietrain (P) crosses have been used for genome-wide linkage and quantitative trait loci (QTL) analysis. Altogether 129 microsatellites, 56 type I loci and 46 trait definitions (specific to growth, fattening, fat deposition, muscling, meat quality, stress resistance and body conformation) were included in the study. In the linkage maps of M × P, W × P and W × M families, average spacing of markers were 18.4, 19.7 and 18.8 cM, the numbers of informative meioses were 582, 534 and 625, and the total lengths of autosomes measured were 27.3, 26.0 and 26.2 Morgan units, respectively. Maternal maps were on average 1.3 times longer than paternal maps. QTLs contributing more than 3% of F2 phenotypic variance could be identified at p < 0.05 chromosome-wide level. Differences in the numbers and positions of QTLs were observed between families. Genome-wide significant QTL effects were mapped for growth and fattening traits on eight chromosomes (1, 2, 4, 13, 14, 17, 18 and X), for fat deposition traits on seven chromosomes (1, 2, 3, 4, 6, 7 and X), for muscling traits on 11 chromosomes (1, 2, 3, 4, 6, 7, 8, 12, 14, 15 and X), for meat quality and stress resistance traits on seven chromosomes (2, 3, 6, 13, 16, 18 and X), and QTLs for body-conformation traits were detected on 14 chromosomes. Closely correlated traits showed similar QTL profiles within families. Major QTL effects for meat quality and stress resistance traits were found on SSC6 in the interval RYR1-A1BG in the W × P and M × P families, and could be attributed to segregation of the RYR1 allele T derived from Pietrain, whereas no effect in the corresponding SSC6 interval was found in family W × M, where Wild Boar and Meishan both contributed the RYR1 allele C. QTL positions were mostly similar in two of the three families for body conformation traits and for growth, fattening, fat deposition and muscling traits, especially on SSC4 (interval SW1073-NGFB). QTLs with large effects were also mapped on SSC7 in the major histocompatibility complex (MHC) (interval CYP21A2-S0102) and affected body length, weight of head and many other traits. The identification of DNA variants in genes causative for the QTLs requires further fine mapping of QTL intervals and a positional cloning. However, for these subsequent steps, the genome-wide QTL mapping in F2 families represents an essential starting point and is therefore significant for animal breeding. Zusammenfassung Drei informative F2 -Familien, die aus Kreuzungen von Europäischem Wildschwein (W), Meishan (M) und Pietrain (P) erstellt worden waren, wurden für eine genomweite Kopplungs- und QTL-Analyse benutzt. Insgesamt wurden 129 Mikrosatellitenloci, 56 Type-I-Loci und 46 Merkmalsdefinitionen (für Wachstum, Mastleistung, Fettansatz, Bemuskelung, Fleischqualität, Stressresistenz und Körperform) in die Untersuchungen einbezogen. In den Kopplungskarten der Familien M × P, W × P und W × M wurden durchschnittliche Markerabstände von 18.4, 19.7 bzw. 18.8 cM erreicht und 582, 534 bzw. 625 informative Meiosen beobachtet. Für die Gesamtlängen der Autosomen wurden in den drei Familien 27.3, 26.0 bzw. 26.2 Morgan-Einheiten gemessen. Die maternalen Kopplungskarten waren durchschnittlich 1.3-fach länger als die paternalen. QTLs, die mehr als 3% der phänotypischen Varianz in der F2 -Generation erklärten, konnten mit p < 0.05 chromosomenweitem Signifikanzniveau nachgewiesen werden. Zwischen den Familien wurden Differenzen in den Anzahlen und Positionen der QTLs beobachtet. Genomweit signifikante QTL-Effekte wurden für Wachstum und Fettansatz auf acht Chromosomen (1, 2, 4, 13, 14, 17, 18 und X) kartiert, für Fettansatz auf sieben Chromosomen (1, 2, 3, 4, 6, 7 und X), für Bemuskelung auf elf Chromosomen (1, 2, 3, 4, 6, 7, 8, 12, 14, 15 und X), für Fleischqualität/Stressresistenz auf sieben Chromosomen (2, 3, 6, 13, 16, 18 und X), und QTLs für die Körperform wurden auf 14 Chromosomen kartiert. Eng korrelierte Merkmale zeigten ähnliche QTL-Profile innerhalb Familien. Die bedeutsamsten QTL-Effekte wurden für Fleischqualitäts- und Stressresistenzmerkmale auf Chromosom 6, Intervall RYR1-A1BG, in den Familien W × P und M × P gefunden, während in diesem Chromosomenintervall in der Familie W × M, in der der RYR1 -Locus keine segregierenden Exon-Allele aufwies, kein QTL zu erkennen war. Mehrere der QTL-Positionen waren für die Körperform wie auch für Wachstum, Mastleistung, Fettansatz und Bemuskelung in zwei von drei Familien ähnlich. Dies galt besonders für Chromosom 4 (Intervall SW1073-NGFB). QTLs mit großen Effekten wurden auf Chromosom 7 im MHC (Intervall CYP21A2-S0102) kartiert; sie beeinflussten Körperlänge, Kopfgewicht, aber auch viele weitere Merkmale. Zur Identifizierung der DNA-Varianten, die einem QTL zugrunde liegen, ist eine Feinkartierung von QTLs und positionale Klonierung erforderlich. Für diese nachfolgenden Untersuchungsmethoden ist jedoch die genomweite QTL-Kartierung in F2 -Familien ein entscheidender Ausgangspunkt; sie ist deshalb bedeutungsvoll für die Tierzüchtung. [source]

Fine Mapping of Polymorphic Alcohol-Related Quantitative Trait Loci Candidate Genes Using Interval-Specific Congenic Recombinant Mice

ALCOHOLISM, Issue 11 2002
Marissa A. Ehringer
Background The inbred long-sleep (ILS) and inbred short-sleep (ISS) strains of mice are widely studied as a model of initial sensitivity to alcohol. Recently, a large comparative DNA sequencing study of candidate genes located within the four Lore quantitative trait loci (QTLs) associated with the ethanol-induced loss of righting reflex in ILS and ISS mice has identified eight genes that contain coding region differences corresponding to amino acid changes. Here, recently developed interval-specific congenic recombinant mice (ISCRs) have been used to map these genes in relationship to newly narrowed QTL regions. Methods Regions of candidate genes containing DNA differences corresponding to previously identified amino acid changes between ISS and ILS mice were amplified from either genomic DNA or complementary DNA from ISCR mice using polymerase chain reaction. The products were purified and directly sequenced to determine the genotypes for each polymorphism. On the basis of these genotypic data, each candidate gene was determined to be located either within or outside of recently narrowed Lore QTL intervals. Results Of these eight candidates with protein-coding differences, five are now excluded from their respective Lore intervals. The other three (Znf142, Ptprn, and Znf133) have been localized to the narrowed QTL intervals. Conclusions These three central nervous system genes (Znf142, Ptprn, and Znf133) represent promising candidates for involvement in the differential sensitivity to alcohol exhibited between ILS and ISS mice. This study also demonstrates how the combination of high-throughput comparative gene sequencing and concomitant genetic fine mapping of QTL regions with ISCRs can be an effective tool for accelerating the process of moving from QTL to gene. [source]