Biomedical subjects

Max F Rothschild

Publications and source records attributed to Max F Rothschild.

15 recordsLinked to original sources

PubMed2006

Investigation of a QTL region for loin eye area and fatness on pig chromosome 1.

Previously, quantitative trait loci (QTL) for tenth-rib backfat (TENTHRIB) and loin eye area (LEA) were identified on pig Chromosome 1 (SSC 1) near microsatellite S0008 from a three-generation Berkshire x Yorkshire cross (BY). This work attempted to refine these QTL positions and identify genes associated with these QTL. Genotypes of BY (n = 555) were determined by PCR-RFLP or PCR tests for 13 polymorphisms identified in BY F(0) individuals for candidate genes, BAC end sequences, and genomic clones. Using least-squares regression interval mapping, the LEA QTL was estimated at S0008; the TENTHRIB QTL position was shifted approximately 1 cM downstream from S0008. Of the genes/sequences mapped in the QTL region, CL349415 was significantly associated with TENTHRIB (p = 0.02) and solute carrier family 2, member 12 (SLC2A12) was significantly associated with LEA (p = 0.02). These results suggest that the gene(s) responsible for the LEA and TENTHRIB QTL effects are tightly linked to S0008 or that the high informativeness of S0008 relative to surrounding markers is influencing the QTL position estimates. In addition, janus kinase 2 (JAK2) was mapped to a suggestive LEA QTL region and showed association with LEA (p = 0.009), fatness, color, and pH traits in BY.

Animals↗

PubMed2006

Inheritance of rupture of the cranial cruciate ligament in Newfoundlands.

OBJECTIVE: To determine prevalence, level of inbreeding, heritability, and mode of inheritance for rupture of the cranial cruciate ligament (RCCL) in Newfoundlands. DESIGN: Retrospective and recruitment study. ANIMALS: 574 client-owned Newfoundlands. PROCEDURE: Medical records from January 1, 1996, to December 31, 2002, were evaluated for prevalence of RCCL. A pedigree was constructed by use of recruited Newfoundlands with RCCL status based on results of veterinary examination; level of inbreeding, heritability, and mode of inheritance were calculated. RESULTS: Hospital prevalence for RCCL was 22%; dogs in the pedigree from the recruitment study had a mean level of inbreeding of 1.19 x 10(4), heritability of 0.27, and a possible recessive mode of inheritance with 51% penetrance for RCCL. CONCLUSIONS AND CLINICAL RELEVANCE: Identification of a genetic basis for RCCL in Newfoundlands provided evidence that investigators can now focus on developing methods to identify carriers to reduce the prevalence of RCCL.

Animals↗

PubMed2005

Estimate of the annual economic impact of treatment of cranial cruciate ligament injury in dogs in the United States.

OBJECTIVE: To estimate the economic impact to veterinary clients for the medical and surgical treatment of rupture of the cranial cruciate ligament (RCCL) in dogs for the year 2003. DESIGN: Economic impact survey. SAMPLE POPULATION: 501 diplomates of the American College of Veterinary Surgeons (ACVS) indicating that their area of surgical emphasis was small animal orthopedic surgery or small animal general and orthopedic surgery and 4,000 veterinarians indicating to the AVMA that their professional area was small animal practice exclusive or mixed animal practice (at least 80% small animal). PROCEDURE: Veterinarians were surveyed concerning the cost for medical and surgical treatment of RCCL for 2003. The economic impact was calculated by multiplying the number of RCCL surgeries performed by the mean cost of surgery. This was added to the number of RCCL cases managed medically multiplied by the mean cost of medical management. This estimate for survey responders was extrapolated to the total number of veterinarians in the study population for the ACVS or AVMA. RESULTS: Estimates for the total cost of surgery were $171,730,134.72 and $1,020,167,907 for veterinarians in the ACVS and AVMA populations, respectively. The cost of medical management was $2,885,687.86 and $126,558,155.16 for veterinarians in the ACVS and AVMA populations, respectively. After combining the ACVS and AVMA populations, we estimated that owners spent $1.32 billion for the treatment of RCCL in the United States in 2003. CONCLUSIONS AND CLINICAL RELEVANCE: RCCL is a prevalent, costly injury. Results may motivate veterinary and consumer agencies to prioritize funding for a better understanding of the injury.

Animals↗

PubMed2005

A QTL resource and comparison tool for pigs: PigQTLDB.

During the past decade, efforts to map quantitative trait loci (QTL) in pigs have resulted in hundreds of QTL being reported for growth, meat quality, reproduction, disease resistance, and other traits. It is a challenge to locate, interpret, and compare QTL results from different studies. We have developed a pig QTL database (PigQTLdb) that integrates available pig QTL data in the public domain, thus, facilitating the use of this QTL data in future studies. We also developed a pig trait classification system to standardize names of traits and to simplify organization and searching of the trait data. These steps made it possible to compare primary data from diverse sources and methods. We used existing pig map databases and other publicly available data resources (such as PubMed) to avoid redundant developmental work. The PigQTLdb was also designed to include data representing major genes and markers associated with a large effect on economically important traits. To date, over 790 QTL from 73 publications have been curated into the database. Those QTL cover more than 300 different traits. The data have been submitted to the Entrez Gene and the Map Viewer resources at NCBI, where the information about markers was matched to marker records in NCBI's UniSTS database. Having these data in a public resource like NCBI allows regularly updated automatic matching of markers to public sequence data by e-PCR. The submitted data, and the results of these calculations, are retrievable from NCBI via Entrez Gene, Map Viewer, and UniSTS. Efforts were undertaken to improve the integrated functional genomics resources for pigs.

Animals↗

PubMed2005

Genetic background influences metabolic response to dietary phosphorus restriction.

Dietary phosphorus (P) is essential to bone growth and turnover; however, little research has focused on the genetic mechanisms controlling P utilization. Understanding the interactions between genetics and dietary P that optimize bone integrity could provide novel interventions for osteoporosis. Thirty-six pigs from two sire lines known to differ in bone structure [heavier boned (HB) and lighter boned (LB)] were assigned to one of the three diets (P adequate, P repletion or P deficient). After 14 days, bone marrow and intact radial bones were collected. Differences between these lines in growth rate, bone integrity and gene expression within bone marrow were observed. In HB, but not LB, pigs, the P-deficient diet decreased weight gain (P<.01). For both lines, P deficiency caused a reduction in radial bone strength (P<.01), but HB P-deficient animals had greater (P<.10) bone integrity than P-deficient LB pigs. In HB, but not LB, pigs, dietary treatment affected the expression of CALCR (calcitonin receptor) (P<.05), VDR (vitamin D receptor) (P<.04) and IGFBP3 (insulin-like growth factor binding protein 3) (P<.06). There was also a trend of increased IL6 (interleukin-6), TFIIB (transcription initiation factor IIB) and SOX9 (sex determining region Y-box 9) expression with P deficiency in HB, but not LB, pigs. Both genetic backgrounds responded similarly to P deficiency with an increase in the expression of OXTR (oxytocin receptor) and IGF1 (insulin-like growth factor 1). Differences in growth rate, bone integrity and gene expression within the bone marrow suggest a difference in the homeorhetic control of P utilization between these genetic lines. Understanding these differences could lead to novel treatments for osteoporosis and aid in the development of tests for identifying those at risk for this disease.

Animals↗

PubMed2005

Relationships between quantitative and reproductive fitness traits in animals.

The relationships between quantitative and reproductive fitness traits in animals are of general biological importance for the development of population genetic models and our understanding of evolution, and of great direct economical importance in the breeding of farm animals. Two well investigated quantitative traits--body weight (BW) and litter size (LS)--were chosen as the focus of our review. The genetic relationships between them are reviewed in fishes and several mammalian species. We have focused especially on mice where data are most abundant. In mice, many individual genes influencing these traits have been identified, and numerous quantitative trait loci (QTL) located. The extensive data on both unselected and selected mouse populations, with some characterized for more than 100 generations, allow a thorough investigation of the dynamics of this relationship during the process of selection. Although there is a substantial positive genetic correlation between both traits in unselected populations, caused mainly by the high correlation between BW and ovulation rate, that correlation apparently declines during selection and therefore does not restrict a relatively independent development of both traits. The importance of these findings for overall reproductive fitness and its change during selection is discussed.

Animals↗

PubMed2005

Combined line-cross and half-sib QTL analysis of crosses between outbred lines.

Data from an F 2 cross between breeds of livestock are typically analysed by least squares line-cross or half-sib models to detect quantitative trait loci (QTL) that differ between or segregate within breeds. These models can also be combined to increase power to detect QTL, while maintaining the computational efficiency of least squares. Tests between models allow QTL to be characterized into those that are fixed (LC QTL), or segregating at similar (HS QTL) or different (CB QTL) frequencies in parental breeds. To evaluate power of the combined model, data wih various differences in QTL allele frequencies (FD) between parental breeds were simulated. Use of all models increased power to detect QTL. The line-cross model was the most powerful model to detect QTL for FD>0.6. The combined and half-sib models had similar power for FD<0.4. The proportion of detected QTL declared as LC QTL decreased with FD. The opposite was observed for HS QTL. The proportion of CB QTL decreased as FD deviated from 0.5. Accuracy of map position tended to be greatest for CB QTL. Models were applied to a cross of Berkshire and Yorkshire pig breeds and revealed 160 (40) QTL at the 5% chromosome (genome)-wise level for the 39 growth, carcass composition and quality traits, of which 72, 54, and 34 were declared as LC, HS and CB QTL. Fourteen CB QTL were detected only by the combined model. Thus, the combined model can increase power to detect QTL and mapping accuracy and enable characterization of QTL that segregate within breeds.

Animals↗

PubMed2004

Polar overdominant inheritance of a DLK1 polymorphism is associated with growth and fatness in pigs.

The polar overdominance model of inheritance was proposed to explain the non-Mendelian expression of callipyge muscular hypertrophy in sheep. The callipyge locus (CLPG) maps to the distal portion of ovine Chromosome 18 within the DLK1- GTL2 region and corresponds to human Chromosome 14q32, where uniparental disomy (UPD) of the region is associated with multiple congenital anomalies, including growth retardation and obesity. We investigated the porcine DLK1- GTL2 region in a cross of two pig breeds to determine if the callipyge polar overdominance is present in another species. Analyses of the parental origin of DLK1 polymorphism in the F2 offspring found that paternal inheritance of DLK1 allele 2 and maternal inheritance of the allele 1 was significantly associated with decreased fat deposition and increased lean muscle mass, while the opposite parental inheritance of these alleles was associated with slower prenatal and postnatal growth. These results suggest that the polar overdominance mode of inheritance is present in the pig chromosomal region that is homologous to the CLPG locus in sheep. Further study in pigs can provide important insights into understanding the molecular regulation of imprinted genes that are associated with human UPD14 and sheep callipyge phenotypes.

Alleles↗

PubMed2004

Porcine genomics delivers new tools and results: this little piggy did more than just go to market.

The past decade has yielded new tools for pig geneticists and breeders thanks to the considerable developments resulting from efforts to map the pig genome. The pig genetic linkage map now has nearly 5000 loci including several hundred genes, microsatellites and amplified fragment length polymorphisms (AFLP) markers. Using tools that include somatic cell hybrid panels and radiation hybrid panels, the physical genetic map is also growing rapidly and has over 4000 genes and markers. Scientists using both exotic and commercial breeds for quantitative trait loci (QTL) scans and candidate gene analyses have identified a number of important chromosomal regions and individual genes associated with growth rate, leanness, feed intake, meat quality, litter size and disease resistance. Using marker-assisted selection (MAS) the commercial pig industry is actively incorporating these gene markers and traditional performance information to improve traits of economic importance in pig production. Researchers now have novel tools including pig gene arrays and advanced bioinformatics that are being exploited to find new candidate genes and to advance the understanding of gene function in the pig. Sequencing of the pig genome has been initiated and further sequencing is now being considered. Advances in pig genomics and directions for future research and the implications to both the pig industry and human health are reviewed.

Agriculture↗

PubMed2004

Investigation of obesity candidate genes on porcine fat deposition quantitative trait loci regions.

OBJECTIVES: To investigate possible obesity candidate genes in regions of porcine quantitative trait loci (QTL) for fat deposition and obesity-related phenotypes. RESEARCH METHODS AND PROCEDURES: Chromosome mapping and QTL analyses of obesity candidate genes were performed using DNA panels from a reference pig family. Statistical association analyses of these genes were performed for fat deposition phenotypes in several other commercial pig populations. RESULTS: Eight candidate genes were mapped to QTL regions of pig chromosomes in this study. These candidate genes also served as anchor loci to determine homologous human chromosomal locations of pig fat deposition QTL. Preliminary analyses of relationships among polymorphisms of individual candidate genes and a variety of phenotypic measurements in a large number of pigs were performed. On the basis of available data, gene-gene interactions were also studied. DISCUSSION: Comparative analysis of obesity-related genes in the pig is not only important for development of marker-assisted selection on growth and fat deposition traits in the pig but also provides for an understanding of their genetic roles in the development of human obesity.

Adipose Tissue↗

PubMed2003

Tests of candidate genes in breed cross populations for QTL mapping in livestock.

In recent years, several F(2) crosses between outbred lines of livestock have been developed to identify quantitative trait loci (QTL). These populations are valuable for further genetic analysis, including positional candidate gene loci (CGL). Analysis of CGL in F(2) populations is, however, hindered by extensive between-breed linkage disequilibrium (LD). The objectives here were to develop and evaluate three tests for CGL in simulated F(2) breed-cross populations. 1) A standard association test, based on the fixed effect of CGL genotype. This test was significant for CGL at considerable distances from the QTL. 2) A marker-assisted association test, based on a test at the CGL of the fixed effect of CGL genotype in a breed-cross QTL interval mapping model. This removed the impact of between-breed LD, but was not powerful in detecting CGL closely linked to the QTL, unless the CGL was the QTL. 3) An F-drop test, comparing F ratios for a QTL at the CGL with and without the CGL included as fixed effect. It had low power to distinguish close from distant CGL. Power to distinguish two CGL within 10 cM from the QTL was limited and little improved by including QTL effects associated with markers to remove between-breed LD, although the power was greater when one of the CGL was the causative mutation. Therefore, while we conclude that candidate gene tests in QTL mapping populations must be interpreted with caution, we now have a clearer picture of the value of candidate gene tests in these populations.

Animals↗

PubMed2003

EST-based gene discovery in pig: virtual expression patterns and comparative mapping to human.

A molecular understanding of porcine reproduction is of biological interest and economic importance. Our Midwest Consortium has produced cDNA libraries containing the majority of genes expressed in major female reproductive tissues, and we have deposited into public databases 21,499 expressed sequence tag (EST) gene sequences from the 3' end of clones from these libraries. These sequences represent 10,574 different genes, based on sequence comparison among these data, and comparison with existing porcine ESTs and genes indicate as many as 4652 of these EST clusters are novel. In silico analysis identified sequences that are expressed in specific pig tissues or organs and confirmed the broad expression in pig for many genes ubiquitously expressed in human tissues. Furthermore, we have developed computer software to identify sequence similarity of these pig genes with their human counterparts, and to extract the mapping information of these human homologues from genome databases. We demonstrate the utility of this software for comparative mapping by localizing 61 genes on the porcine physical map for Chromosomes (Chrs) 5, 10, and 14.

Algorithms↗

PubMed2002

Molecular cloning, expression pattern and chromosomal mapping of pig CD69.

CD69 is a type II membrane protein belonging to C-type lectin family receptor, and expressed on activated leukocytes. Pig CD69 was cloned by RT-PCR using degenerate primers. Pig CD69 cDNA contains a 600 bp open reading frame with its predicted polypeptide sequence of 200 amino acids. Pig CD69 has 75%, 67%, and 57% sequence identity with cow, human, and mouse CD69, respectively. A splicing isoform, which lacks exon 2 encoding the transmembrane domain, was detected. Pig CD69 gene is located on Chromosome (Chr) 5q25 where the NKG2D gene was mapped. In RT-PCR analysis, pig CD69 mRNA was detected in activated PBL, NK cells, macrophages, monocytes, and granulocytes, but not in resting cells. The inducers for CD69 gene expression were PMA, PHA, LPS, G7 mAb, PNK-E mAb, PM16-6 mAb and the K562 cell line. Moreover, CD69 mRNA is expressed in bone marrow, spleen, thymus and lymph nodes but not in muscle, mammary gland, or the pig kidney cell line (LLC-PK(1)). These results indicate that pig Chr 5q25 contains the NK gene complex and CD69 can be used as an activation marker in pig cells of innate as well as acquired immune systems.

Amino Acid Sequence↗

PubMed2002

The pig platelet-activating factor receptor gene is expressed at the mRNA level in different tissues and is mapped to chromosome 6.

After the pig platelet-activating factor receptor (PAFr) gene was cloned and sequenced, the chromosomal location of this gene was studied using a pig/rodent somatic cell hybrid panel containing 27 cell lines. The results indicated that the pig PAFr gene is located on SSC6q22-23. Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is thought to be very important in the animal reproductive processes. Its function is mediated through a membrane-bound receptor. Pig PAFr mRNA distribution in different tissues was tested using reverse transcription and PCR (RT-PCR) reactions. All tissues examined expressed PAFr. Using a pig PAFr gene DNA competitor, PAFr expression was quantificated. The pig PAFr mRNA expression level was estimated to be from 1 x 10(2) to 1.2 x 10(4) copies of complementary DNA (cDNA) per 50 ng of total RNA. The highest level was found in lung, and the lowest in the skeletal muscle. These results demonstrated that PAFr was differentially expressed in pig tissues.

Animals↗

PubMed2002

Application of the false discovery rate to quantitative trait loci interval mapping with multiple traits.

Controlling the false discovery rate (FDR) has been proposed as an alternative to controlling the genome-wise error rate (GWER) for detecting quantitative trait loci (QTL) in genome scans. The objective here was to implement FDR in the context of regression interval mapping for multiple traits. Data on five traits from an F2 swine breed cross were used. FDR was implemented using tests at every 1 cM (FDR1) and using tests with the highest test statistic for each marker interval (FDRm). For the latter, a method was developed to predict comparison-wise error rates. At low error rates, FDR1 behaved erratically; FDRm was more stable but gave similar significance thresholds and number of QTL detected. At the same error rate, methods to control FDR gave less stringent significance thresholds and more QTL detected than methods to control GWER. Although testing across traits had limited impact on FDR, single-trait testing was recommended because there is no theoretical reason to pool tests across traits for FDR. FDR based on FDRm was recommended for QTL detection in interval mapping because it provides significance tests that are meaningful, yet not overly stringent, such that a more complete picture of QTL is revealed.

Animals↗