Assignment of the SIAT4A gene to bovine chromosome 14 by linkage mapping of an associated microsatellite.
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Alleles↗
Biomedical subjects
B Murdoch
Publications and source records attributed to B Murdoch.
Identification of three microsatellite loci on bovine chromosome 19.
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Alleles↗
Assessment of positional candidate genes myf5 and igf1 for growth on bovine chromosome 5 in commercial lines of Bos taurus.
Quantitative trait loci for growth traits in beef cattle have been previously reported and fine-mapped in three chromosomal regions of 0 to 30 cM, 55 to 70 cM, and 70 to 80 cM of bovine chromosome 5. In this study, we further examined the association between gene-specific single nucleotide polymorphisms (SNP) of two positional candidate genes, bovine myogenic factor 5 (myf5) and insulin-like growth factor-1 (igf1), in the QTL regions and the birth weight (BWT), preweaning average daily gain (PWADG), and average daily gain on feed (ADGF) in commercial lines of Bos taurus. The QTL regions for the growth traits identified using a haplotype association analysis, which included the gene-specific SNP markers for both genes in this study, were in agreement with previous studies. The gene-specific SNP marker association analysis indicated that the SNP in myf5 had a significant additive effect on PWADG in the M1 line of Beefbooster Inc. (P < 0.10), and a significant additive effect (P < 0.05) and a significant dominance effect (P < 0.10) on ADGF in the M3 line of Beefbooster Inc. When the data from the two commercial lines were pooled, the SNP in myf5 showed a significant association with PWADG (P < 0.10) and with ADGF (P < 0.05). The association between the SNP and BWT, however, did not reach a significance level in the M1 line, the M3 line, or across the lines. For igf1, no significant association between the SNP and the growth traits was detected in either the M1 line or the M3 line, whereas there was only a significant dominance effect (P < 0.10) on BWT detected for the SNP in igfl when the data from the two commercial lines were pooled. These results suggest that myf5 is a strong candidate gene that influences PWADG and ADGF in beef cattle. The SNP of igf1 may not be a causative or close to the causative mutation that affects the three growth traits in the populations of beef cattle examined in this study. Other SNP of igf1 and myf5 or other genes in their respective chromosomal regions, however, should also be studied.
Alleles↗
Identification and fine mapping of quantitative trait loci for growth traits on bovine chromosomes 2, 6, 14, 19, 21, and 23 within one commercial line of Bos taurus.
We report the identification and fine mapping of QTL for birth weight (BWT), preweaning ADG (PWADG), and postweaning ADG on feed (ADGF) in a commercial line of Bos taurus using an identical-by-descent haplotype sharing method. One hundred seventy-six calves of 12 bulls (9 to 30 male calves from each sire) of the Beefbooster, Inc., M1 line were typed using 71 genetic markers from bovine chromosomes (BTA) 2, 6, 14, 19, 21, and 23 (8 to 16 markers from each chromosome). Sixteen haplotypes were found to have significant (P <0.05) associations with BWT at the comparison-wise threshold. The 16 haplotypes span 13 chromosomal regions, two on BTA 2 (9.1 to 22.5 cM and 95.0 to 100.3 cM), three on BTA 6 (8.2 to 11.8 cM, 35.5 to 49.7 cM, and 83.0 to 86.2 cM), three on BTA 14 (26.0 to 26.7 cM, 36.2 to 46.2 cM, and 52.0 to 67.7 cM), one on BTA 19 (52.0 to 52.7 cM), two on BTA 21 (9.9 to 20.4 cM and 28.2 to 46.1 cM), and two on BTA 23 (23.9 to 36.0 cM and 45.1 to 50.9 cM). Thirteen haplotypes spanning seven chromosomal regions significantly affected (P <0.05) PWADG at the comparison-wise threshold. The seven chromosomal regions include two regions on BTA 6 (11.8 to 44.2 cM and 83.0 to 86.2 cM), one on BTA 14 (26.7 to 50.8 cM), one on BTA 19 (4.8 to 15.9 cM), one on BTA 21 (9.9 to 20.4 cM), and two on BTA 23 (17.3 to 36.0 cM and 45.1 to 50.9 cM). For ADGF, 11 haplotypes were identified to have significant associations (P <0.05) at the comparison-wise threshold. The 11 haplotypes represented eight chromosomal regions, one on BTA 2 (9.1 to 22.5 cM), two on BTA 6 (49.7 to 50.1 cM and 59.6 to 63.6 cM), two on BTA 14 (17.0 to 24.0 cM and 36.2 to 46.2 cM), two on BTA 19 (52.0 to 52.7 cM and 65.1 to 65.7 cM), and one on BTA 21 (46.1 to 53.1 cM). The QTL regions identified and fine mapped in this study will provide a reference for future positional candidate gene research and marker-assisted selection of various growth traits.
Alleles↗
Identification and fine mapping of quantitative trait loci for backfat on bovine chromosomes 2, 5, 6, 19, 21, and 23 in a commercial line of Bos taurus.
Backfat thickness is one of the major quantitative traits that affects carcass quality in beef cattle. In this study, we identified and fine-mapped QTL for backfat EBV on bovine chromosomes 2, 5, 6, 19, 21, and 23 using an identical-by-descent haplotype-sharing analysis in a commercial line of Bos taurus. Eleven haplotypes were found to have significant associations with backfat EBV at the comparison-wise P-value threshold, and one at the chromosome-wise P-value threshold on bovine chromosomes 5, 6, 19, 21, and 23. On average, the 12 significant haplotypes had an effect of 0.62 SD on backfat EBV, ranging from 0.38 SD to 1.33 SD. The 12 significant haplotypes spanned nine chromosomal regions, one on chromosome 5 (65.4 to 70.0 cM), three on 6 (8.2 to 11.8 cM, 63.6 to 68.1 cM, and 81.5 to 83.0 cM), three on 19 (4.8 to 15.9 cM, 39.4 to 46.5 cM, and 65.7 to 99.5 cM), one on 21 (46.1 to 53.1 cM), and one on 23 (45.1 to 50.9 cM). Among the nine chromosomal regions, six were new QTL regions and three showed remarkable agreement with QTL regions that were previously reported. Eight of the nine QTL regions were localized to less than or close to 10 cM in genetic distance. The results provide a useful reference for further positional candidate gene research and marker-assisted selection for backfat.
Adipose Tissue↗
Different measures of energetic efficiency and their phenotypic relationships with growth, feed intake, and ultrasound and carcass merit in hybrid cattle.
Residual feed intake (RFI) has been proposed as an index for determining beef cattle energetic efficiency. Although the relationship of RFI with feed conversion ratio (FCR) is well established, little is known about how RFI compares to other measures of efficiency. This study examined the phenotypic relationships among different measures of energetic efficiency with growth, feed intake, and ultrasound and carcass merit of hybrid cattle (n = 150). Dry matter intake, ME intake (MEI), ADG, metabolic weight (MWT), and FCR during the test averaged 10.29 kg/d (SD = 1.62), 1,185.45 kJ/(kg0.75 x d) (SD = 114.69), 1.42 kg/d (SD = 0.25), 86.67 kg0.75 (SD = 10.21), and 7.27 kg of DM/kg of gain (SD = 1.00), respectively. Residual feed intake averaged 0.00 kg/d and ranged from -2.25 kg/d (most efficient) to 2.61 kg/d (least efficient). Dry matter intake (r = 0.75), MEI (r = 0.83), and FCR (r = 0.62) were correlated with RFI (P < 0.001) and were higher for animals with high (>0.5 SD) RFI vs. those with medium (+/-0.5 SD) or low (<0.5 SD) RFI (P < 0.001). Partial efficiency of growth (PEG; energetic efficiency for ADG) was correlated with RFI (r = -0.89, P < 0.001) and was lower (P < 0.001) for high- vs. medium- or low-RFI animals. However, RFI was not related to ADG (r = -0.03), MWT (r = -0.02), relative growth rate (RGR; growth relative to instantaneous body size; r = -0.04), or Kleiber ratio (KR; ADG per unit of MWT; r = -0.004). Also, DMI was correlated (P < 0.01) with ADG (r = 0.66), MWT (r = 0.49), FCR (r = 0.49), PEG (r = -0.52), RGR (r = 0.18), and KR (r = 0.36). Additionally, FCR was correlated (P < 0.001) with ADG (r = -0.63), PEG (r = -0.83), RGR (r = -0.75), and KR (r = -0.73), but not with MWT (r = 0.07). Correlations of measures of efficiency with ultrasound or carcass traits generally were not different from zero except for correlations of RFI, FCR, and PEG, respectively, with backfat gain (r = 0.30, 0.20, and -0.30), ultrasound backfat (r = 0.19, 0.21, and -0.25), grade fat (r = 0.25, 0.19, and -0.27), lean meat yield (r = -0.22, -0.18, and 0.24), and yield grade (r = 0.28, 0.24, and -0.25). These phenotypic relationships indicate that, compared with other measures of energetic efficiency, RFI should have a greater potential to improve overall production efficiency and PEG above maintenance, and lead to minimal correlated changes in carcass merit without altering the growth and body size of different animals.
Adipose Tissue↗
Fine mapping of quantitative trait loci and assessment of positional candidate genes for backfat on bovine chromosome 14 in a commercial line of Bos taurus.
Backfat thickness is one of the major quantitative traits that affect carcass quality in beef cattle. In this study, we have fine mapped a QTL for backfat EBV on bovine chromosome 14, using an identical-by-descent haplotype-sharing analysis, in a commercial line of Bos taurus. We also examined the association between gene-specific single nucleotide polymorphism (SNP) markers of the genes diacylgcerol acyltransferase 1 (DGAT1) and thyroglobulin (TG) and the backfat EBV. The results indicate that the QTL region for backfat identified on chromosome 14 is in agreement with previous studies. However, neither of the two polymorphisms of candidate genes tested, DGAT1 nor TG, showed a significant (P > 0.10) association with the backfat EBV in the cattle populations examined. However, a strong association (P = 0.0058) was detected between a microsatellite marker (CSSM66) lying approximately mid-way between the two candidate genes and the backfat EBV. These results suggest that other SNP of DGAT1, TG, or other gene(s) in the chromosomal region should be examined to test whether they have a significant effect on lipid metabolism.
Acyltransferases↗
The identification of common haplotypes on bovine chromosome 5 within commercial lines of Bos taurus and their associations with growth traits.
The cosegregation between a genetic marker and the QTL in a well-designed mapping population is the basis for successful QTL mapping. Linkage disequilibria are, however, also expected among individuals that descended from the same breeding line, and some common haplotypes should carry on and segregate among individuals of the line. These identical by descent haplotypes make it possible to identify and locate the QTL segregating in the line. We report the identification of common haplotypes within commercial lines of Bos taurus and their associations with growth traits. One hundred and seventy six male calves and their 12 sires (9 to 30 male calves of each sire) of the Beefbooster, Inc., M1 line selected for maternal traits over 30 yr were genotyped using 16 microsatellite markers chosen from bovine chromosome 5 for the initial haplotype and growth association analysis. In order to verify the results from the M1 line, another 170 male calves and their 14 sires from the Beefbooster M3 line were genotyped using nine microsatellite markers chosen from bovine chromosome 5. The alleles of each male calf contributed by the sire and by the dam were identified, and haplotypes in the M1 line were established along 93% of bovine chromosome 5. The haplotypes in the M3 line were established along the chosen regions of bovine chromosome 5. Regression analysis detected 10 haplotypes in three chromosomal regions (0 to 30 cM, 55 to 70 cM, and 70 to 80 cM) that showed significant associations with birth weight, preweaning average daily gain, and average daily gain on feed in M1 line and 9 haplotypes associated with the growth traits in the same chromosomal regions in the M3 line at the comparisonwise threshold level. On average, the 19 haplotypes have an effect of 0.68 SD on the growth traits, ranging from 0.41 SD to 1.02 SD The results provide a useful reference for further positional candidate gene research and marker-assisted selection.
Alleles↗
Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells.
Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (h Delta-1) and h Delta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that h Delta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human. (Blood. 2001;97:1960-1967)
Adaptor Proteins, Signal Transducing↗
Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation.
A pool of stem cells that arise from the mesoderm during embryogenesis initiates hematopoiesis. However, factors that regulate the expansion of blood stem cells are poorly understood. We show here that cytokine-induced proliferation of primitive human hematopoietic cells could be inhibited with antibodies to hedgehog (Hh). Conversely, Sonic hedgehog (Shh) treatment induced the expansion of pluripotent human hematopoietic repopulating cells detected in immunodeficient mice. Noggin, a specific inhibitor of bone morphogenetic protein 4 (BMP-4), was capable of inhibiting Shh-induced proliferation in a similar manner to anti-Hh; however, anti-Hh had no effect on BMP-4-induced proliferation. Our study shows that Shh functions as a regulator of primitive hematopoietic cells via mechanisms that are dependent on downstream BMP signals.
Base Sequence↗
Circulating hematopoietic stem cells serve as novel targets for in utero gene therapy.
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Adult↗
[Coefficients between TEOAEs and DPOAEs in infants].
OBJECTIVE: To investigate the coefficients of TEOAEs and DPOAEs based on various pass/fail criteria. METHOD: Thirty-six Australia infants were tested (age range: 1-6 months) using both TEOAE and DPOAE. Cohen's Kappa (K) were used to analyze different criteria. RESULT: There is a significant low agreement in the screening outcomes between TEOAEs and DPOAEs, and different criteria for TEOAEs. CONCLUSION: The findings from the study of coefficients among commonly used screening pass/fail criteria suggested that there is no simple relationship among them. The possible reasons for weak agreement were discussed.
Cochlea↗
The human hematopoietic stem cell compartment is heterogeneous for CXCR4 expression.
The chemokine stromal derived factor-1alpha (SDF-1alpha) has been implicated recently in the chemotaxis of primitive human hematopoietic cells, suggesting that pluripotent human stem cells express the SDF-1alpha receptor, CXCR4. By using flow cytometry and confocal microscopy, we have identified and isolated primitive subsets of human CXCR4(+) and CXCR4(-) cells. Distinctions in the progenitor content and response to SDF-1alpha in vitro indicate that CXCR4(+) and CXCR4(-) cells represent discrete populations of primitive blood cells. The i.v. transplantation of these subfractions into immune-deficient mice established that both possess comparable engraftment capacity in vivo. Human myeloid, lymphoid, and primitive CD34(+) CXCR4(+) cells were present in chimeric animals transplanted with either subset, indicating that CXCR4(+) and CXCR4(-) stem cells have equivalent proliferative and differentiative abilities. Our study indicates that the human stem cell compartment is heterogeneous for CXCR4 expression, suggesting that the relationship between CXCR4 expression and stem cell repopulating function is not obligatory.
Animals↗
G protein-coupled receptor kinase-mediated desensitization of metabotropic glutamate receptor 1A protects against cell death.
Metabotropic glutamate receptors (mGluRs) constitute a unique subclass of G protein-coupled receptors (GPCRs) that bear little sequence homology to other members of the GPCR superfamily. The mGluR subtypes that are coupled to the hydrolysis of phosphoinositide contribute to both synaptic plasticity and glutamate-mediated excitotoxicity in neurons. In the present study, the expression of mGluR1a in HEK 293 cells led to agonist-independent cell death. Since G protein-coupled receptor kinases (GRKs) desensitize a diverse variety of GPCRs, we explored whether GRKs contributed to the regulation of both constitutive and agonist-stimulated mGluR1a activity and thereby may prevent mGluR1a-mediated excitotoxicity associated with mGluR1a overactivation. We find that the co-expression of mGluR1a with GRK2 and GRK5, but not GRK4 and GRK6, reduced both constitutive and agonist-stimulated mGluR1a activity. Agonist-stimulated mGluR1a phosphorylation was enhanced by the co-expression of GRK2 and was blocked by two different GRK2 dominant-negative mutants. Furthermore, GRK2-dependent mGluR1a desensitization protected against mGluR1a-mediated cell death, at least in part by blocking mGluR1a-stimulated apoptosis. Our data indicate that as with other members of the GPCR superfamily, a member of the structurally distinct mGluR family (mGluR1a) serves as a substrate for GRK-mediated phosphorylation and that GRK-dependent "feedback" modulation of mGluR1a responsiveness protects against pathophysiological mGluR1a signaling.
Amino Acid Sequence↗
The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells.
The Notch ligand, Jagged-1, plays an essential role in tissue formation during embryonic development of primitive organisms. However, little is known regarding the role of Jagged-1 in the regulation of tissue-specific stem cells or its function in humans. Here, we show that uncommitted human hematopoietic cells and cells that comprise the putative blood stem cell microenvironment express Jagged-1 and the Notch receptors. Addition of a soluble form of human Jagged-1 to cultures of purified primitive human blood cells had modest effects in augmenting cytokine-induced proliferation of progenitors. However, intravenous transplantation of cultured cells into immunodeficient mice revealed that human (h)Jagged-1 induces the survival and expansion of human stem cells capable of pluripotent repopulating capacity. Our findings demonstrate that hJagged-1 represents a novel growth factor of human stem cells, thereby providing an opportunity for the clinical utility of Notch ligands in the expansion of primitive cells capable of hematopoietic reconstitution.
Animals↗
Identification of novel circulating human embryonic blood stem cells.
Using murine models, primitive hematopoietic cells capable of repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded by stem cells migrating through fetal circulation and would serve as ideal targets for in utero cellular therapy. In humans, however, it is unknown whether similar stem cells exist. Here, we identify circulating hematopoeitic cells present during human in utero development that are capable of multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution analysis, the frequency of these fetal stem cells was found to be 1 in 3.2 x 10(5), illustrating a 3- and 22-fold enrichment compared with full-term human cord blood and circulating adult mobilized-peripheral blood, respectively. Comparison of in vivo differentiation and proliferative capacity demonstrated that circulating fetal stem cells are intrinsically distinct from hematopoietic stem cells found later in human development and those derived from the fetal liver or fetal bone marrow compartment at equivalent gestation. Taken together, these studies demonstrate the existence of unique circulating stem cells in early human embryonic development that provide a novel and previously unexplored source of pluripotent stem cell targets for cellular and gene-based fetal therapies. (Blood. 2000;96:1740-1747)
ADP-ribosyl Cyclase↗
Isolation and characterization of human CD34(-)Lin(-) and CD34(+)Lin(-) hematopoietic stem cells using cell surface markers AC133 and CD7.
Recent evidence indicates that human hematopoietic stem cell properties can be found among cells lacking CD34 and lineage commitment markers (CD34(-)Lin(-)). A major barrier in the further characterization of human CD34(-) stem cells is the inability to detect this population using in vitro assays because these cells only demonstrate hematopoietic activity in vivo. Using cell surface markers AC133 and CD7, subfractions were isolated within CD34(-)CD38(-)Lin(-) and CD34(+)CD38(-)Lin(-) cells derived from human cord blood. Although the majority of CD34(-)CD38(-)Lin(-) cells lack AC133 and express CD7, an extremely rare population of AC133(+)CD7(-) cells was identified at a frequency of 0.2%. Surprisingly, these AC133(+)CD7(-) cells were highly enriched for progenitor activity at a frequency equivalent to purified fractions of CD34(+) stem cells, and they were the only subset among the CD34(-)CD38(-)Lin(-) population capable of giving rise to CD34(+) cells in defined liquid cultures. Human cells were detected in the bone marrow of non-obese/severe combined immunodeficiency (NOD/SCID) mice 8 weeks after transplantation of ex vivo-cultured AC133(+)CD7(-) cells isolated from the CD34(-)CD38(-)Lin(-) population, whereas 400-fold greater numbers of the AC133(-)CD7(-) subset had no engraftment ability. These studies provide novel insights into the hierarchical relationship of the human stem cell compartment by identifying a rare population of primitive human CD34(-) cells that are detectable after transplantation in vivo, enriched for in vitro clonogenic capacity, and capable of differentiation into CD34(+) cells. (Blood. 2000;95:2813-2820)
AC133 Antigen↗
Paediatric hearing screening in the community: a comparison of outcomes from transient evoked and distortion product otoacoustic emission measures.
The present study aimed to compare TEOAE screening outcomes based on different pass/fail criteria and the outcomes from TEOAE and DPOAE measures in children. For the purpose of the study, the subjects were divided into two age groups: group 1 (n = 36; mean age 2.7 months, SD 1.2), and group 2 (n = 29; mean age 37.5 months, SD 16.3). Results indicated that the agreement of screening outcomes between pass/fail criteria for the TEOAE measure and between TEOAE and DPOAE measures was significantly lower for the younger group than for the older group. The greater variability in the younger age group could be partly attributed to the higher physiological noise produced by young infants. Irrespective of the pass/fail criteria used, the findings of the present study suggest that the OAE outcomes for children with weak OAEs or OAEs obscured by excessive noise were most variable.
Acoustic Stimulation↗