SNP detection and linkage mapping for pig genes involved in growth.
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Animals↗
Biomedical subjects
M F Rothschild
Publications and source records attributed to M F Rothschild.
Mapping of 21 genetic markers to a QTL region for meat quality on pig chromosome 17.
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Animals↗
Association of MITF with white spotting in Beagle crosses and Newfoundland dogs.
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Animals↗
Liver X receptor alpha and beta genes have the potential role on loin lean and fat content in pigs.
Liver X receptor alpha (LXRA) and beta (LXRB) are members of the nuclear receptor subfamily and are important regulators of genes involved in lipid, fatty acid and glucose metabolism in liver, and adipose tissue as well as in skeletal muscle. To investigate whether the two LXR genes play a role in influencing lean and fat growth in pigs, we discovered and examined two polymorphisms in LXRA (LXRA Bsl in exon 2, and LXRA HpyCH4 III in intron 8) and one polymorphism in LXRB (LXRB Aci I in exon 5) for genetic linkage and association analyses. Linkage analyses using a three-generation resource family of a cross between the Berkshire and Yorkshire (BY) pig breeds assigned LXRA to SSC2 and LXRB to SSC6. Association analyses were carried out among those polymorphisms and traits evaluated in the BY F(2) family and four pig commercial populations. These analyses indicated that the LXRA HpyCH4 III polymorphism was significantly associated with loin eye area and total lipid in individuals from the BY family. Significant associations were also found between Bsl I polymorphism in LXRA and boneless loin (%), as well as marbling score in one commercial line. The LXRB Aci I polymorphism was significantly associated with lean meat and fat content in the BY family and a number of the commercial lines examined. Our current findings suggested that LXRA and LXRB might have potential effects, especially for loin lean and fat content.
Adipose Tissue↗
Prospecting for pig single nucleotide polymorphisms in the human genome: have we struck gold?
Gene-to-gene variation in the frequency of single nucleotide polymorphisms (SNPs) has been observed in humans, mice, rats, primates and pigs, but a relationship across species in this variation has not been described. Here, the frequency of porcine coding SNPs (cSNPs) identified by in silico methods, and the frequency of murine cSNPs, were compared with the frequency of human cSNPs across homologous genes. From 150,000 porcine expressed sequence tag (EST) sequences, a total of 452 SNP-containing sequence clusters were found, totalling 1394 putative SNPs. All the clustered porcine EST annotations and SNP data have been made publicly available at http://sputnik.btk.fi/project?name=swine. Human and murine cSNPs were identified from dbSNP and were characterized as either validated or total number of cSNPs (validated plus non-validated) for comparison purposes. The correlation between in silico pig cSNP and validated human cSNP densities was found to be 0.77 (p < 0.00001) for a set of 25 homologous genes, while a correlation of 0.48 (p < 0.0005) was found for a primarily random sample of 50 homologous human and mouse genes. This is the first evidence of conserved gene-to-gene variability in cSNP frequency across species and indicates that site-directed screening of porcine genes that are homologous to cSNP-rich human genes may rapidly advance cSNP discovery in pigs.
Animals↗
Single nucleotide polymorphism identification, linkage and radiation hybrid mapping of the porcine pituitary adenylate cyclase-activating polypeptide type I receptor gene to chromosome 18.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with diverse biological actions. Type I PACAP receptors (PACAPR) are specific for PACAP, whereas type II and III PACAPRs are less restricted. To localize and analyse the variation of this gene, a 559-bp long intronic fragment of the porcine PACAPR gene was amplified by polymerase chain reaction and sequenced in samples from five different pig breeds. One single nucleotide polymorphism was identified and its allele frequency was determined in all five breeds. Linkage analysis in a Berkshire x Yorkshire reference family placed the PACAPR gene on chromosome 18, between SW787 and S0062 (SW787- 8.1 cM -PACAPR- 3.0 cM -S0062). Radiation hybrid mapping confirmed that the PACAPR gene was linked to SW1682 on chromosome 18 (28.8 cR(3000); LOD = 10.4).
Animals↗
Evidence of breed-dependent differences in susceptibility to porcine circovirus type-2-associated disease and lesions.
Porcine circovirus type 2 (PCV2) has been confirmed as the primary cause of postweaning multisystemic wasting syndrome (PMWS). However, in the field, PMWS is seen only in a small percentage of pigs infected with PCV2. The overall objective of the study reported here was to determine whether host genetic differences in the susceptibility to PCV2-associated disease exist among selected breeds of pigs. This study included Duroc (n = 23), Landrace (n = 19), and Large White (n = 21) pigs. The pigs were infected intranasally and intramuscularly at 5-7 weeks of age with PCV2. A portion of the pigs (31/63; 30.2%) had low passively acquired PCV2 antibodies at the time of infection. There were no differences in mean weight gain, rectal temperature, or respiratory score. Clinical disease compatible with PMWS was observed only in the Landrace pigs. Most of the PCV2-infected pigs had enlarged lymph nodes, and individual Duroc and Landrace pigs had mottled tan lungs. PCV2-associated lymphoid depletion and granulomatous inflammation were observed in pigs of all breeds. Three of 19 Landrace pigs and none of the Duroc or Large White pigs developed severe lymphoid lesions associated with large amounts of intralesional PCV2 antigen typical of PMWS. Compared with seronegative Landrace pigs, Landrace pigs that had low maternal antibodies at the time of PCV2 inoculation had significantly (P < 0.05) less-severe PCV2-associated lesions. The results suggest a predisposition of the Landrace pigs of this study to PCV2-induced disease and lesions, and that low levels of passively acquired antibodies are protective.
Animals↗
An investigation of susceptibility to porcine reproductive and respiratory syndrome virus between two genetically diverse commercial lines of pigs.
The objective of this study was to determine whether host genetics play a role in susceptibility to the respiratory disease in growing pigs caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Based on a previous study, 2 genetically diverse commercial lines of pigs that also were divergent in the susceptibility of monocyte-derived macrophages to PRRSV infection in vitro were selected for an in vivo challenge study. Based on the average percentage of infected macrophages for each line, a line derived from the Large White breed was characterized as fluorescence-activated cell sorting(hi) (FACS(hi)), and a line derived from Duroc and Pietrain breeds was characterized as FACS(lo). Pigs from each line were challenged at 6 wk of age with PRRSV VR-2385 and necropsied at 10 or 21 d after infection. Data collected included clinical evaluation of disease, virus titration in serum and lung lavage fluid, macroscopic lung lesion scores, and microscopic lung lesion scores. The FACS(lo) line had consistently more severe clinical disease compared with the FACS(hi) line in the early stages of infection. Differences between line means were significant (P < 0.05) at 10 d after infection for all variables just described, and the FACS(lo) line showed more severe signs of disease. By 21 d after infection, clinical signs and lesions were resolving, and the differences between lines were significant (P < 0.04) only for microscopic lung lesion scores but approached significance (P < 0.08) for virus titer in serum. At 21 d after infection, the relationship between the lines reversed; the FACS(hi) line had higher serum virus titers than the FACS(lo) line. This report provides evidence that strongly suggests the existence of a host genetic component in disease susceptibility to PRRSV and indicates that further study is warranted to define the cellular mechanisms that affect disease susceptibility.
Animals↗
Optimal haplotype structure for linkage disequilibrium-based fine mapping of quantitative trait loci using identity by descent.
A linkage disequilibrium-based method for fine mapping quantitative trait loci (QTL) has been described that uses similarity between individuals' marker haplotypes to determine if QTL alleles are identical by descent (IBD) to model covariances among individuals' QTL alleles for a mixed linear model. Mapping accuracy with this method was found to be sensitive to the number of linked markers that was included in the haplotype when fitting the model at a putative position of the QTL. The objective of this study was to determine the optimal haplotype structure for this IBD-based method for fine mapping a QTL in a previously identified QTL region. Haplotypes consisting of 1, 2, 4, 6, or all 10 available markers were fit as a "sliding window" across the QTL region under ideal and nonideal simulated population conditions. It was found that using haplotypes of 4 or 6 markers as a sliding "window" resulted in the greatest mapping accuracy under nearly all conditions, although the true IBD state at a putative QTL position was most accurately predicted by IBD probabilities obtained using all markers. Using 4 or 6 markers resulted in greater discrimination of IBD probabilities between positions while maintaining sufficient accuracy of IBD probabilities to detect the QTL. Fitting IBD probabilities on the basis of a single marker resulted in the worst mapping accuracy under all conditions because it resulted in poor accuracy of IBD probabilities. In conclusion, for fine mapping using IBD methods, marker information must be used in a manner that results in sensitivity of IBD probabilities to the putative position of the QTL while maintaining sufficient accuracy of IBD probabilities to detect the QTL. Contrary to expectation, use of haplotypes of 4-6 markers to derive IBD probabilities, rather than all available markers, best fits these criteria. Thus for populations similar to those simulated here, optimal mapping accuracy for this IBD-based fine-mapping method is obtained with a haplotype structure including a subset of all available markers.
Crosses, Genetic↗
In vitro susceptibility of macrophages to porcine reproductive and respiratory syndrome virus varies between genetically diverse lines of pigs.
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be responsible for financial losses in the swine industry worldwide. It remains undetermined whether genetic variability of the host in susceptibility to PRRSV exists and if this variability can be exploited to help control this important disease. The objective of this study was to determine if an in vitro flow cytometry (FACS) assay that detects the percentage of monocyte-derived macrophages (MDM) infected with PRRSV could be utilized to demonstrate genetic variability in the susceptibility between distinct lines of pigs. Over 400 growing pigs from six genetic lines maintained in a single commercial breeding herd were screened using an in vitro FACS assay. From this initial screening, two genetically diverse lines of pigs that were also divergent in their FACS results were selected for further study. An additional 264 pigs from these two lines were subsequently tested for in vitro susceptibility to PRRSV. As in the preliminary screening, the Large White line had significantly higher average percent positive MDM over the Duroc-Pietrain synthetic line. This report suggests a genetic component for susceptibility to PRRSV exists and that the in vitro assay may be useful in predicting the relative susceptibility to PRRSV in large groups of animals.
Animals↗
Mapping and association studies of diabetes related genes in the pig.
The mitogen-activated protein kinase 8 (MAPK8), resistin (RETN), 11 beta hydroxysteroid dehydrogenase isoform 1 (HSD11B1) and protein kinase B Akt2 (AKT2) genes are all genes known to affect insulin signalling and have been implicated in the progression of obesity and type 2 diabetes in humans. In this study, polymorphisms in the porcine diabetes related MAPK8, RETN, HSD11B1 and AKT2 genes were identified, mapped and their associations with phenotypic measurements in swine were analysed. Polymorphisms detected in the MAPK8, RETN and HSD11B1 loci were used to genotype a Berkshire-Yorkshire pig breed reference family. Using linkage analysis, RETN, HSD11B1 and MAPK8 genes were mapped to pig chromosomes 2, 9 and 14, respectively, while the AKT2 gene was physically mapped to pig chromosome 6q21. Results presented here suggest associations between the polymorphisms in the MAPK8, RETN and HSD11B1 genes with several phenotypic measurements, including fat deposition traits in the pig. Because these genes have been implicated in obesity and diabetes in humans, and this study suggests associations with fat related traits, further research on these genes in swine may provide useful information on genetic factors underlying lean pork production.
11-beta-Hydroxysteroid Dehydrogenases↗
SNP analysis of AMY2 and CTSL genes in Litopenaeus vannamei and Penaeus monodon shrimp.
Genetic studies in shrimp have focused on disease, with production traits such as growth left unexamined. Two shrimp species, Litopenaeus vannamei and Penaeus monodon, which represent the majority of US shrimp imports, were selected for single nucleotide polymorphism (SNP) discovery in alpha-amylase (AMY2) and cathepsin-l (CTSL), both candidate genes for growth. In L. vannamei, four SNPs were found in AMY2 and one SNP was found in CTSL. In P. monodon, one SNP was identified in CTSL. The CTSL gene was mapped to linkage group 28 of P. monodon using the female map developed with the Australian P. monodon mapping population. Association analyses for the AMY2 and CTSL genes with body weight (BW) were performed in two L. vannamei populations. While neither gene was found to be significantly associated with BW in these populations, there was a trend in one population towards higher BW for allele G of CTSL SNP C681G.
Animals↗
Mapping of 443 porcine EST improves the comparative maps for SSC1 and SSC7 with the human genome.
Numerous mapping studies of complex traits in the pig have resulted in quantitative trait loci (QTL) intervals of 10-20 cM. To improve the chances to identify the genes located in such intervals, increased expressed sequence tags (EST)-based marker density, coupled with comparative mapping with species whose genomes have been sequenced such as human and mouse, is the most efficient tool. In this study, we mapped 443 porcine EST with a radiation hybrid (RH) panel (384 had LOD > 6.0) and a somatic cell hybrid panel. Requiring no discrepancy between two-point and multipoint RH data allowed robust assignment of 309 EST, of which most were located on porcine chromosomes (SSC) 1, 4, 7, 8 and X. Moreover, we built framework maps for two chromosomes, SSC1 and SSC7, with mapped QTL in regions with known rearrangement between pig and human genomes. Using the Blast tool, we found orthologies between 407 of the 443 pig cDNA sequences and human genes, or to existing pig genes. Our porcine/human comparative mapping results reveal possible new homologies for SSC1, SSC3, SSC5, SSC6, SSC12 and SSC14 and add markers in synteny breakpoints for chromosome 7.
Animals↗
SNP detection and association analyses of candidate genes for rupture of the cranial cruciate ligament in the dog.
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Animals↗
Joint analysis of two breed cross populations in pigs to improve detection and characterization of quantitative trait loci.
The purpose of this study was to develop and implement least squares interval-mapping models for joint analysis of breed cross QTL mapping populations and to evaluate the effect of joint analysis on QTL detected for economic traits in data from two breed crosses in pigs. Data on 26 growth, carcass composition, and meat quality traits from F2 crosses between commercially relevant pig breeds were used: a Berkshire x Yorkshire cross at Iowa State University (ISU) and a Berkshire x Duroc cross at the University of Illinois (UOI). All animals were genotyped for a total of 39 (ISU) and 32 (UOI) markers on chromosomes 2, 6, 13, and 18. Marker linkage maps derived from the individual and joint data were similar with regard to order and relative position, but some differences in absolute distances existed. Maps from the joint data were used in all analyses. The individual and joint data sets were analyzed using several least squares interval-mapping models: line-cross (LC) models with Mendelian and parent-of-origin effects; halfsib models (HS); and combined models (CB) that included LC and HS effects. Lack-of-fit tests between the models were used to characterize QTL for mode of expression and to identify segregation of QTL within parental breeds. A total of 26 (8), 47 (18), and 53 (16) QTL were detected at the 5% chromosome (genome)-wise level in the ISU, UOI, and joint data for the 26 analyzed traits. Of the 53 QTL detected in the joint data, only six were detected in both populations and for many, allele effects differed between the two crosses. Despite the lack of overlap between the two populations, joint analysis resulted in an increase in significance for many QTL, including detection of ten QTL that did not reach significance in either population. Confidence intervals for position also were smaller for several QTL. In contrast, 24 QTL, most of which were detected at chromosome-wise levels in the ISU or UOI population, were not detected in the joint data. Presence of paternally expressed QTL near the IGF2 region of SSC2 was confirmed, with major effects on backfat and loin muscle area, particularly in the UOI population, as well as one or more QTL for carcass composition in the distal arm of Chromosome 6. Results of this study suggest that joint analysis using a range of QTL models increases the power of QTL mapping and QTL characterization, which helps to identify genes for subsequent marker-assisted selection.
Animals↗
Expeditor: a pipeline for designing primers using human gene structure and livestock animal EST information.
We have developed software, called Expeditor, that can be used to combine known gene structure information from human and coding sequence information from farm animal species for a streamlined primer design in target farm animal species. This software has many utilities, which include PCR-based SNP discovery for identification of genes/markers associated with economically important traits in farm animals, comparative mapping analysis, and evolution studies. The use of this software helps minimize tedious manual operations and reduces the chance of errors by more conventional approaches.
Animals↗
Functional and phylogenetic analyses of a melanocortin-4 receptor mutation in domestic pigs.
The melanocortin-4 receptor (MC4R), a G protein-coupled seven-transmembrane receptor, which is expressed in the brain, plays an important role in the control of mammalian energy homeostasis. A missense mutation (Asp298Asn) was identified in the porcine MC4R gene, which is associated with growth and food intake traits. The Asn298 mutation occurs within a highly conserved motif, NPLIY, of all members of G protein-coupled receptors; whereas, Asp298 is conserved in all five melanocortin receptor subtypes. Functional analysis of the porcine MC4R variant was performed with an in vitro gene expression system in 293 cells. Ligand binding (NDP-alphaMSH) did not differ between Asp298 and Asn298 MC4R proteins. However, the Asn298 MC4R variant was unable to stimulate cAMP production in response to NDP-alphaMSH stimulation; whereas, the Asp298 variant could stimulate cAMP accumulation. These results demonstrate that the Asp298 is required for normal MC4R signaling to the adenylyl cyclase. Sequencing of the MC4R gene of seven diverse genera within the Suiformes that include Hippopotamidae (hippos), Tayassuidae (peccaries) and Suidae (pigs), revealed 62 nucleotide variations in MC4R. Phylogenetic relationships of MC4R variations are consistent with those previously described from morphological and physiological data among the subfamilies of the Suiformes. These findings revealed that a single missense mutation (Asp298Asn) of aspartic acid (Asp) to asparagine (Asn) in MC4R gene decreased cAMP content and MC4R signaling, but with no difference in the ligand binding was associated with growth and feed intake traits in domestic pigs.
Adenylyl Cyclases↗
Investigation of a peroxisome proliferator-activated receptor gamma haplotype effect on meat quality and carcass traits in pigs.
Peroxisome proliferator-activated receptor gamma (PPARG) is a key transcription factor that controls adipocyte differentiation and fat deposition in mammals. The primary goal of this study was to investigate PPARG as a candidate gene for meat quality and carcass traits in swine. Part of the PPARG promoter, along with the most 5'-proximal exon of the gene, was amplified by PCR and subsequently screened for polymorphisms by sequencing. A Met59Val substitution was detected in the porcine PPARG gene along with four polymorphisms in the promoter region of the adipose-specific PPARG2. Three of these polymorphisms were chosen for genotyping and tested for association with meat quality, carcass and growth traits, according to the candidate gene approach. More than 1500 animals from different lines and populations were used in the study with records for meat quality and carcass traits. No convincing associations were found between the traits investigated and the PPARG genotypes. It does not appear that variation at the PPARG locus is affecting meat quality, carcass or growth traits in the pig populations studied.
Animals↗