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Biomedical subjects

Xiao-Lin Wu

Publications and source records attributed to Xiao-Lin Wu.

14 recordsLinked to original sources
PubMed2006

Overexpression of PTEN suppresses growth and induces apoptosis by inhibiting the expression of survivin in bladder cancer cells.

The tumor suppressor gene PTEN, which encodes a multifunctional phosphatase protein, is mutated in a variety of human cancers. Several reports have indicated that it has growth-suppressive and proapoptosis properties and displayed an altered expression pattern during human oncogenesis. Overexpression of PTEN leads to decreasing cell growth and tumorigenicity in vitro and in vivo. In the present study, we further demonstrated that overexpression of PTEN mediated by adenovirus suppressed bladder cancer cell growth and significantly induced apoptosis, through downregulating of survivin and activating of caspase cascades. Our results indicate that Ad-PTEN exerts its tumor suppressive effect on bladder cancer cells through inhibiting survivin and upregulating caspase-related proteins. Thus Ad-PTEN may be potentially therapeutic for the treatment of bladder cancers.

Adenoviridae↗
PubMed2006

A simplified QTL mapping approach for screening and mapping of novel AFLP markers associated with beef marbling.

Genome screening of quantitative trait loci (QTL) for a complex trait is usually costly and highly laborious, as it requires a large number of markers spanning the whole genome. Here we present a simplified approach for screening and mapping of QTL-linked markers for beef marbling using a WagyuxLimousin F(2) reference population. This simplified approach involves integration of the amplified fragment length polymorphism (AFLP) with DNA pooling and selective genotyping and comparative bioinformatics tools. AFLP analysis on two high and two low marbling DNA pools yielded ten visually different markers. Among them, four were confirmed based on individual AFLP validation. Sequencing and in silico characterization assigned two of these AFLP markers to bovine chromosomes 1 (BTA1) and 13 (BTA13), which are orthologous to human chromosomes HSA21q22.2 and HSA10p11.23 with both regions harboring QTL for obesity-related phenotypes. Both AFLP markers showed significantly large additive genetic effects (0.28+/-0.11 on BTA1 and 0.54+/-0.21 on BTA13) on beef-marbling score (BMS) (P<0.05). Overall, this approach is less time consuming, inexpensive and in particular, suitable for screening and mapping QTL-linked markers when targeting one or a few complex traits.

Animals↗
PubMed2006

A novel nuclear-encoded mitochondrial poly(A) polymerase PAPD1 is a potential candidate gene for the extreme obesity related phenotypes in mammals.

People with obesity, especially extreme obesity, are at risk for many health problems. However, the responsible genes remain unknown in >95% of severe obesity cases. Our previous genome-wide scan of Wagyu x Limousin F2 cattle crosses with extreme phenotypes revealed a molecular marker significantly associated with intramuscular fat deposition. Characterization of this marker showed that it is orthologous to the human gene KIAA1462 located on HSA10p11.23, where a major quantitative trait locus for morbid obesity has been reported. The newly identified mitochondrial poly(A) polymerase associated domain containing 1 (PAPD1) gene, which is located near this marker, is particularly interesting because the polymerase is required for the polyadenylation and stabilization of mammalian mitochondrial mRNAs. In the present study, both cDNA and genomic DNA sequences were annotated for the bovine PAPD1 gene and ten genetic markers were detected in the promoter and exon 1 region. Among seven markers assayed on approximately 250 Wagyu x Limousin F2 animals, two single nucleotide polymorphisms (SNPs) in the promoter region were significantly associated with intramuscular fat (P<0.05). However, there was a significant interaction (P<0.05) between a third SNP, which causes an amino acid change in coding exon 1, and each of these two promoter SNPs on intramuscular fat deposition. In particular, the differences between double heterozygous animals at two polymorphic sites and the slim genotype animals exceeded 2.3 standard deviations for the trait in both cases. Our study provides evidence for a new mechanism--the involvement of compound heterosis in extreme obesity, which warrants further examination.

Adipose Tissue↗
PubMed2005

Evaluation of candidate gene effects for beef backfat via Bayesian model selection.

Candidate gene approaches provide tools for exploring and localizing causative genes affecting quantitative traits and the underlying variation may be better understood by determining the relative magnitudes of effects of their polymorphisms. Diacyglycerol O-acyltransferase 1 (DGAT1), fatty acid binding protein (heart) 3 (FABP3), growth hormone 1 (GH1), leptin (LEP) and thyroglobulin (TG) have been previously identified as genes contributing to genetic control of subcutaneous fat thickness (SFT) in beef cattle. In the present research, Bayesian model selection was used to evaluate effects of these five candidate genes by comparing competing non-nested models and treating candidate gene effects as either random or fixed. The analyses were implemented in SAS to simplify the programming and computation. Phenotypic data were gathered from a F(2) population of Wagyu x Limousin cattle. The five candidate genes had significant but varied effects on SFT in this population. Bayesian model selection identified the DGAT1 model as the one with the greatest model probability, whether candidate gene effects were considered random or fixed, and DGAT1 had the greatest additive effect on SFT. The SAS codes developed in the study are freely available and can be downloaded at: http://www.ansci.wsu.edu/programs/.

Adiposity↗
PubMed2005

Pattern profiling and mapping of the fat body transcriptome in Drosophila melanogaster.

In Drosophila, the fat body is a collective name for the masses and sheets of adipose tissue that are distributed throughout the fly body. Thus far, >386,000 Drosophila expressed sequence tags (ESTs) have been deposited to the GenBank database, including 10,443 derived from fat body in flies (data accessed on October 7, 2004). The objective of this study was to map the transcriptome of the fat body in flies and thus provide genomics and bioinformatics tools for developing a Drosophila model for addressing the genetic complexity of obesity in humans. The gene-EST Basic Local Alignment Search Tool (BLAST) matches revealed that these ESTs could represent 12,188 coding genes in the Drosophila genome. Among them, at least 2,261 are expressed in the fat body, including 41 identified as preferentially expressed genes with logarithm of odds >3.0. Self-organizing map analysis revealed a cluster of 290 genes favorably expressed in the fat body compared with genes expressed in five other tissues. Mapping of the fat body transcriptome identified a 1.7-Mb domain on 3L containing 35 genes that were expressed at a much higher level than in other tissues (transcript density factor = 1.0 approximately 2.3).

Animals↗
PubMed2004

Census of orthologous genes and self-organizing maps of biologically relevant transcriptional patterns in chickens (Gallus gallus).

The launch of large-scale chicken expressed sequence tags (EST) projects has placed the chicken in the lead for the number of EST sequences in agriculturally important animals. More than 451,000 chicken ESTs derived from over 158 libraries have been deposited in the NCBI dbEST database as of December 2003. But how many genes these ESTs represent and how they are expressed in different chicken tissues/organs remain undetermined. In the present research, we developed a human gene-based strategy for census of chicken orthologous genes and identification of their expression patterns. Among 34,157 human coding genes used in the study, BLAST analysis revealed that 11,066 genes provisionally matched 248,628 chicken ESTs. Based on the average EST abundance of the orthologous genes, the current public repository of chicken ESTs could represent approximately 20,000 provisional genes. Analysis of gene expression in 14 single tissues/organs showed that approximately 15% of genes were expressed exclusively in single tissue/organ whereas the remaining approximately 85% of genes were co-expressed in two or more tissues/organs. A majority (91.15%) of genes expressed in chicken embryos were also expressed at post-hatch stages, indicating that most genes activated in chicken embryos could serve housekeeping functions. Self-organizing maps (SOM) analysis organized 8807 provisional genes in selected chicken tissues into 98 clusters with each cluster being indicative of common regulatory factors and pathways. A total of 969 provisional orthologous genes were identified as preferentially expressed genes (PEGs) in various chicken tissues/organs (LOD>3.0). No doubt, the present study on gene expression patterns will provide insight into dynamics of metabolic pathways and tissue/organ programming and reprogramming in chickens.

Algorithms↗
PubMed2004

Optimal sampling of a population to determine QTL location, variance, and allelic number.

In a population intended for breeding and selection, questions of interest relative to a specific segregating QTL are the variance it generates in the population, and the number and effects of its alleles. One approach to address these questions is to extract several inbreds from the population and use them to generate multiple mapping families. Given random sampling of parents, sampling strategy may be an important factor determining the power of the analysis and its accuracy in estimating QTL variance and allelic number. We describe appropriate multiple-family QTL mapping methodology and apply it to simulated data sets to determine optimal sampling strategies in terms of family number versus family size. Genomes were simulated with seven chromosomes, on which 107 markers and six QTL were distributed. The total heritability was 0.60. Two to ten alleles were segregating at each QTL. Sampling strategies ranged from sampling two inbreds and generating a single family of 600 progeny to sampling 40 inbreds and generating 40 families of 15 progeny each. Strategies involving only one to five families were subject to variation due to the sampling of inbred parents. For QTL where more than two alleles were segregating, these strategies did not sample QTL alleles representative of the original population. Conversely, strategies involving 30 or more parents were subject to variation due to sampling of QTL genotypes within the small families obtained. Given these constraints, greatest QTL detection power was obtained for strategies involving five to ten mapping families. The most accurate estimation of the variance generated by the QTL, however, was obtained with strategies involving 20 or more families. Finally, strategies with an intermediate number of families best estimated the number of QTL alleles. We conclude that no overall optimal sampling strategy exists but that the strategy adopted must depend on the objective.

Alleles↗
PubMed2004

Comparative gene-based in silico analysis of transcriptomes in different bovine tissues and (or) organs.

A gene-based approach was used to annotate 322,168 cattle expressed sequence tags (ESTs) based on human genes in order to census the transcriptomes, analyze their expression similarities, and identify genes preferentially expressed in different bovine tissues and (or) organs. Of the 34,157 human coding genes used in a standalone BLAST search, 14,928 could be matched with provisional orthologous sequences in a total of 230,135 bovine ESTs. The remaining 92,033 bovine ESTs were estimated to represent an additional 5970 genes in cattle. On average, approximately 8600 genes were estimated to be expressed in a single tissue and (or) organ and 13,000 in a pooled tissue library. On the basis of the estimated numbers of genes, no more than 3% of genes would be missed when approximately 34,000 ESTs were sequenced from a single tissue and (or) organ library and approximately 40,000 ESTs from a pooled source, respectively. Cluster analyses of the gene expression patterns among 12 single tissues and (or) organs in cattle revealed that their expression similarities would depend on physiological functions. In addition, a total of 1502 genes were identified as preferentially expressed genes in these 12 single tissues and (or) organs with LOD (logarithm of the odds, base 10) > or = 3.0. Therefore, our study provides some insights for further investigating the developmental and functional relations of various tissues and organs in mammals.

Animals↗
PubMed2004

[Genetic linkage between Atrn gene and microsatellite markers and the effects to some economic traits in pigs].

The genetic polymorphisms of Atrn gene, which were from 174 F0-F5 Danish resource family pigs (DRF) that has undergone five successive generations of inbreeding and 129 F9 Hunan yellow pigs (HY) that were developed by crossbreeding, were tested by PCR-RFLP method, and the effects to carcass and growth traits were also analyzed. The results showed that: (1) Three genotypes of AA, AB, BB were detected by Taq I-RFLP in the two pig breeds, and highly significant differences (P<0.01) in genotype frequencies were found between the two breeds; (2) Based on the linkage analysis of resource family pigs using CRI-MAP V2.4 software, Atrn gene loci in DRF was found to be linked with SW1031 loci on chromosome 17, the recombination frequency and LOD score for Atrn gene were 0.21 and 3.19 respectively; (3) With the least square analysis of multi-variable model, the significant differences among Atrn genotypes were found in ADSG and ABF traits in DRF and also in ADG, ABF and LMP traits in HY (P<0.05 or P<0.01), BB genotype pigs were superior to AA or AB genotype pigs. Based on the above mentioned results, B gene has favorable effects in important economic traits, and thus selection to BB genotype will get favorable effects in important economic traits. This will provide theory basis for Atrn gene being regarded as a candidate gene in pig carcass and growth traits.

Animals↗
PubMed2004

[Achievements and applications in making chicken chimeras using BCs].

The technology of producing chicken chimeras using blastodermal cells is very important not only in the field of transgenic chicken bioreactor but also in searching for efficient ways to conserve avian genetic resource. The basic processes for producing chicken chimeras consist of: (1) Setting up the color model; (2) Separating and dissociating of donor embryos; (3) Compromising of the recipient embryos; (4) Windowing and recovering the recipient eggs; (5) Cells injecting; (6) Method of hatching. The progress, obstacles and prospects of producing chicken chimeras via BCs were discussed in this paper.

Animals↗
PubMed2003

Estimating allelic number and identity in state of QTLs in interconnected families.

When multiple related families derived from inbred lines are jointly analysed to detect quantitative trait loci (QTLs), the analysis should estimate allelic effects as accurately as possible and estimate the probability that different parents carry alleles that are identical in state. Analyses exist that assume that all parents carry unique alleles or that all parents but one carry the same allele. In practice, many configurations are possible that group different parents according to their identity-in-state condition at a putative QTL allele. Here, we propose a variable model Bayesian analysis that selects among possible identity-in-state configurations and jointly estimates the allelic effects of identical-in-state parents. We contrast this analysis with a fixed model analysis that estimates unique allelic effects for all parents. We analyse two simulated mating designs: an experimental design in which three inbred parents were crossed to generate two families of 150 doubled haploid lines; and a breeding design in which 20 inbred parents were crossed to generate 60 families of 20 doubled haploid lines, with each parent contributing to six families. In all cases where some parents were simulated to carry alleles of identical effect (that is, they were identical in state), the variable analysis estimated allelic effects with lower mean-squared error than the fixed analysis. The variable analysis showed that, unless each family contains many individuals (more than 100), there is insufficient information in DNA-marker and phenotypic data to determine with high probability the QTL allelic number.

Bayes Theorem↗
PubMed2003

[Progress in Attractin(mahogany/ATRN) gene].

Attractin is an autosomal recessive gene and received great attention within the last few decades. Attractin in different lines has been identified attractin to have multiple roles in regulating physiological process. It affects the balance between agonist and antagonist at receptors on melanocytes, modifies behaviour and basal metabolic rate, intervenes developing the central nervous system and its function, and modulates an interaction between activated T cell and macrophages. The attractin gene encodes a protein that is involved in the suppression of diet-induced obesity, its expression level in the brain has a significant relationship with obesity, the role indicates the therapeutic potential of attractin in the treatment of obesity. Furthermore, the murine attractin locus is located in a region harboring several QTL for body weight and fatness. In this paper, we review the research development of mahogany, introduce the related gene and gene mapping, and summarize its regulating mechanism in the physiological process. Additionally,the further research on the gene is also suggested.

English Abstract↗
PubMed2002

[A search for chromosome 13 QTL in a complex pig family].

A search for chromosome 13 QTL was carried out in a pig family of complex pedigree. The results indicated that a significant QTL on chromosome 13 was segregating in pig family. The QTL significantly affected body weight and average daily gain (P < 0.05), but the effect on backfat thickness was not significant (P > 0.05). Interval mapping localized this QTL between SW1898 and SW398. The estimated linkage position of this QTL was 75.2 cM. The QTL variance estimated at the marker interval was 0.9037 for the body weight and 0.0010 for average daily gain, respectively. This was the region which flanked the PIT1 gene, an essential transcriptional regulatory factor of growth hormone, prolactin and thyrotropin beta subunit. The present result confirmed a previous suggestion of a QTL for early growth traits at the estimated PIT1 position, and further implied that the effect of PIT1 genes on growth and body weight remained for the whole period of individual growth and development. Aditional evidence was also found which suggested a backfat QTL on chromosome 13, at a location approximately 28.3-63.4 cM apart from the one for body weight and growth, but the level of significance was not consistent in different generations.

Animals↗