Showing papers by "Stephen J. O'Brien published in 2003"
TL;DR: The largest available molecular data set for placental mammals is investigated, which includes segments of 19 nuclear and three mitochondrial genes for representatives of all extant placental orders and permits simultaneous constraints from the fossil record and allows rates of molecular evolution to vary on different branches of a phylogenetic tree.
Abstract: Competing hypotheses for the timing of the placental mammal radiation focus on whether extant placental orders originated and diversified before or after the Cretaceous-Tertiary (K/T) boundary. Molecular studies that have addressed this issue suffer from single calibration points, unwarranted assumptions about the molecular clock, and/or taxon sampling that lacks representatives of all placental orders. We investigated this problem using the largest available molecular data set for placental mammals, which includes segments of 19 nuclear and three mitochondrial genes for representatives of all extant placental orders. We used the Thorne/Kishino method, which permits simultaneous constraints from the fossil record and allows rates of molecular evolution to vary on different branches of a phylogenetic tree. Analyses that used different sets of fossil constraints, different priors for the base of Placentalia, and different data partitions all support interordinal divergences in the Cretaceous followed by intraordinal diversification mostly after the K/T boundary. Four placental orders show intraordinal diversification that predates the K/T boundary, but only by an average of 10 million years. In contrast to some molecular studies that date the rat–mouse split as old as 46 million years, our results show improved agreement with the fossil record and place this split at 16–23 million years. To test the hypothesis that molecular estimates of Cretaceous divergence times are an artifact of increased body size subsequent to the K/T boundary, we also performed analyses with a “K/T body size” taxon set. In these analyses, interordinal splits remained in the Cretaceous.
786 citations
TL;DR: The HLA associations with progression to AIDS that have been consistently affirmed are reviewed and the underlying mechanisms behind some of these associations are discussed based on functional studies of immune cell recognition.
Abstract: Genetic resistance to infectious diseases is likely to involve a complex array of immune-response and other genes with variants that impose subtle but significant consequences on gene expression or protein function. We have gained considerable insight into the genetic determinants of HIV-1 disease, and the HLA class I genes appear to be highly influential in this regard. Numerous reports have identified a role for HLA genotype in AIDS outcomes, implicating many HLA alleles in various aspects of HIV disease. Here we review the HLA associations with progression to AIDS that have been consistently affirmed and discuss the underlying mechanisms behind some of these associations based on functional studies of immune cell recognition.
777 citations
TL;DR: The inferred multiple origins and independent historical elevation in population frequency of felid melanistic mutations suggest the occurrence of adaptive evolution of this visible phenotype in a group of related free-ranging species.
287 citations
TL;DR: Novel therapies for patients with GS are required as the frequency, presenting characteristics, and survival in patients with nonleukemic GS are described by conducting a review of all untreated patients presenting to the MD Anderson Cancer Center between January 1990 and June 2002.
Abstract: Granulocytic sarcoma (GS) is an extramedullary tumor composed of immature myeloid cells The objectives of this study were to describe the frequency, presenting characteristics, and survival in patients with nonleukemic GS by conducting a review of all untreated patients presenting to the MD Anderson Cancer Center between January 1990 and June 2002 In all, 21 patients with nonleukemic GS, 1520 patients with acute myeloid leukemia (AML), and 402 patients with high-risk myelodysplastic syndrome (MDS) were identified GS occurred in 14% of patients with AML, and 11% of patients with AML or high-risk MDSs The median patient age was 57 years (range, 7-81) Among 20 patients with available cytogenetics in tissue and/or bone marrow, six had chromosome 8 abnormalities The median follow-up of surviving patients is 12 months (range, 7-75) In all, 20 patients were treated Patients were treated with AML-type chemotherapy (n=16), chemotherapy and radiotherapy (n=3), or radiotherapy alone (n=1) A total of 13 patients (65%) achieved complete remission and one patient (5%) achieved partial remission The median overall survival was 20 months (range, 1-75), median overall failure-free survival was 12 months (range, 1-75) The median survival of patients with chromosome 8 abnormalities was 12 months compared with 40 months of those without (P=017) Novel therapies for patients with GS are required
194 citations
TL;DR: The genome organization of the chemokine receptor and HLA gene clusters and their influence on the HIV/AIDS epidemic provides compelling evidence for the interaction of infectious and genetic diseases in recent human history.
Abstract: The polymorphisms within the human genome include several functional variants that cause debilitating inherited diseases. An elevated frequency of some of these deleterious mutations can be explained by a beneficial effect that confers a selective advantage owing to disease resistance in carriers of such mutations during an infectious disease outbreak. We here review plausible examples of balanced functional polymorphisms and their roles in the defense against pathogens. The genome organization of the chemokine receptor and HLA gene clusters and their influence on the HIV/AIDS epidemic provides compelling evidence for the interaction of infectious and genetic diseases in recent human history.
170 citations
TL;DR: The associations with class I alleles are consistent with a previously implicated role for CD8-mediated cytolytic-T-cell response in determining the outcome of an acute HBV infection.
Abstract: Following an acute hepatitis B virus (HBV) infection, clearance or persistence is determined in part by the vigor and breadth of the host immune response. Since the human leukocyte antigen system (HLA) is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are key determinants of viral clearance. HLA class I and II genes were molecularly typed in 194 Caucasian individuals with viral persistence and 342 matched controls who had cleared the virus. A single class I allele, A*0301 (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.30 to 0.72; P = 0.0005) was associated with viral clearance. The class II allele DRB1*1302 was also associated with clearance (OR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03), but its significance decreased in a multivariate model that included other alleles associated with disease outcome as covariates. B*08 was associated with viral persistence both independently (OR, 1.59; 95% CI, 1.04 to 2.43; P = 0.03) and as part of the conserved Caucasian haplotype A*01-B*08-DRB1*03. The B*44-Cw*1601 (OR, 2.23; 95% CI, 1.13 to 4.42; P = 0.02) and B*44-Cw*0501 (OR, 1.99; 95% CI, 1.22 to 3.24; P = 0.006) haplotypes were also associated with viral persistence. Interestingly, both the B*08 haplotype and DR7, which forms a haplotype with B*44-Cw*1601, have been associated with nonresponse to the HBV vaccine. The associations with class I alleles are consistent with a previously implicated role for CD8-mediated cytolytic-T-cell response in determining the outcome of an acute HBV infection.
138 citations
TL;DR: The pathognomonic radiographic and magnetic resonance imaging triad of posterior acetabular lip fracture, iliofemoral ligament disruption, and hemarthrosis defines traumatic posterior hip subluxation and patients in whom osteonecrosis is diagnosed at six weeks are at risk for collapse and joint degeneration, and they are advised against returning to sports.
Abstract: Background: Traumatic posterior hip subluxation is a potentially devastating injury that is often misdiagnosed as a simple hip sprain or strain. The purpose of the present study was to outline the injury mechanism, pathoanatomy, clinical and radiographic findings, and treatment of traumatic hip subluxation in an athletic population.
Methods: Over a nine-year period, eight participants in American football who had sustained a traumatic posterior hip subluxation were evaluated and treated. The injury mechanism, clinical findings, and radiographic findings were reviewed. The mean duration of follow-up was thirty-four months.
Results: The most common mechanism of injury was a fall on a flexed, adducted hip. Physical examination revealed painful limitation of hip motion. Initial radiographs demonstrated a characteristic posterior acetabular lip fracture. Initial magnetic resonance images revealed disruption of the iliofemoral ligament, hemarthrosis, and a viable femoral head. Two players were treated acutely with hip aspiration, and all eight players were treated with a six-week regimen of toe-touch weight-bearing with use of crutches. Six players recovered and returned to the previous level of competition. Two players had development of severe osteonecrosis and ultimately required total hip arthroplasty.
Conclusion: The pathognomonic radiographic and magnetic resonance imaging triad of posterior acetabular lip fracture, iliofemoral ligament disruption, and hemarthrosis defines traumatic posterior hip subluxation. Patients in whom large hemarthroses are diagnosed on magnetic resonance images should undergo acute aspiration, and all players should be treated with a six-week regimen of toe-touch weight-bearing with use of crutches. Patients who have no sign of osteonecrosis on magnetic resonance imaging at six weeks can safely return to sports activity. Patients in whom osteonecrosis is diagnosed at six weeks are at risk for collapse and joint degeneration, and they should be advised against returning to sports.
Level of Evidence: Prognostic study, Level IV (case series). See Instructions to Authors for a complete description of levels of evidence.
122 citations
TL;DR: The integrated linkage and RH maps reveal approximately 110 conserved segments ordered between the human and feline genomes, and provide extensive anchored reference marker homologues that connect to the more gene dense human and mouse sequence maps, suitable for positional cloning applications.
Abstract: We report construction of second-generation integrated genetic linkage and radiation hybrid (RH) maps in the domestic cat (Felis catus) that exhibit a high level of marker concordance and provide near-full genome coverage. A total of 864 markers, including 585 coding loci (type I markers) and 279 polymorphic microsatellite loci (type II markers), are now mapped in the cat genome. We generated the genetic linkage map utilizing a multigeneration interspecies backcross pedigree between the domestic cat and the Asian leopard cat (Prionailurus bengalensis). Eighty-one type I markers were integrated with 247 type II markers from a first-generation map to generate a map of 328 loci (320 autosomal and 8 X-linked) distributed in 47 linkage groups, with an average intermarker spacing of 8 cM. Genome coverage spans approximately 2,650 cM, allowing an estimate for the genetic length of the sex-averaged map as 3,300 cM. The 834-locus second-generation domestic cat RH map was generated from the incorporation of 579 type I and 255 type II loci. Type I markers were added using targeted selection to cover either genomic regions underrepresented in the first-generation map or to refine breakpoints in human/feline synteny. The integrated linkage and RH maps reveal approximately 110 conserved segments ordered between the human and feline genomes, and provide extensive anchored reference marker homologues that connect to the more gene dense human and mouse sequence maps, suitable for positional cloning applications.
109 citations
TL;DR: Comparison of the feline MHC with the murine and human MHC offers a detailed view of the consequences of genome organization in three mammalian lineages.
Abstract: To study comparative molecular dynamics in the genesis of the major histocompatibility complex (MHC), we determined a complete nucleotide sequence spanning 758,291 bp of the domestic cat (Felis catus) extended and classical class II region. The feline class II MHC includes 44 genes (31 predicted to be expressed) which display DNA sequence homology and ordered gene synteny with human HLA and mouse H2, in extended class II and centromere proximal regions (DM to DO) of the classical class II region. However, remarkable genomic alterations including gene gain and loss plus size differentials of 250 kb are evident in comparisons of the cat class II with those of human and mouse. The cat MHC lacks the entire DQ region and retains only relict pseudogene homologs of DP genes, compensated by expansion and reorganization of seven modern DR genes. Repetitive gene families within the feline MHC comprise 35% of the feline MHC with very different density and abundance of GC levels, SINES, LINES, STRs, and retro-elements from the same repeats in human and mouse MHC. Comparison of the feline MHC with the murine and human MHC offers a detailed view of the consequences of genome organization in three mammalian lineages.
105 citations
TL;DR: The results suggest that elevated serum IL10 or the IL10 promoter -592 C/C genotype are associated with development of AIDS lymphoma.
102 citations
TL;DR: Breeding success and reproductive traits for many endemic felids in Latin American zoos appear to be suboptimal, and likely would benefit from improvements in diet and exhibitry.
Abstract: Reproductive evaluations were conducted on 185 male cats representing eight endemic Latin American species that were maintained in 44 zoos and private facilities in 12 Latin American countries. Reproductive assessments (testicular measures, ejaculate quality, and blood testosterone/cortisol concentration) were used to establish normative values for large- and small-sized cats in Latin American collections. Data also were analyzed using multiple regression to study the impact of proven breeder status, diet, and various animal housing combinations. Most felids (>95%) in the survey were of wild-born origin, and 50% of males had low sperm counts (<1 million total sperm per ejaculate). Among large cats (jaguars and pumas), proven breeders had larger (P<0.05) testes, greater semen volume, and more normal sperm than nonbreeders. Males on adequate diets had higher (P<0.05) circulating cortisol. Among small-sized felids, proven breeders had higher (P<0.05) testosterone, and males housed alone or paired with a conspecific female had more (P<0.05) total sperm per ejaculate and greater (P<0.05) seminal and testicular volumes. Fifty-nine ejaculates (potentially representing ∼100 artificial insemination (AI) or 26,000 in vitro fertilization (IVF) procedures) were cryopreserved for a felid genome resource bank. In conclusion, breeding success and reproductive traits for many endemic felids in Latin American zoos appear to be suboptimal, and likely would benefit from improvements in diet and exhibitry. Technology transfer and continued training of zoo staff and scientists in Latin American countries are essential if these zoos are to achieve their tremendous conservation potential for felids and other threatened endemic species. Zoo Biol 22:421–441, 2003. © 2003 Wiley-Liss, Inc.
TL;DR: Although the extensive linkage disequilibrium precludes positive identification of the causal variant, the results suggest that genetic variation in the H7 region influences susceptibility to HIV-1 infection.
Abstract: Background MCP-1 (CCL2), MCP-3 (CCL7), and eotaxin (CCL11) are genes for CC chemokines clustered on the long arm of chromosome 17. Previous studies have implicated these chemokines in monocyte recruitment, viral replication, and anti-HIV cytotoxic T cell responses. An epidemiological analysis identified genetic variants influencing HIV-1 transmission and disease progression. Methods Genomic DNA from over 3000 participants enrolled in five natural history cohorts in the United States were analyzed. Nine single nucleotide polymorphisms (SNP) covering 33 kb containing these three genes were genotyped using the polymerase chain reaction. Distortions in allele, genotype, and haplotype frequencies were assessed with respect to HIV-1 transmission and rates of disease progression using categorical and survival analyses. Results Extensive linkage disequilibrium was observed. Three SNP (-2136T located in the MCP-1 promoter region, 767G in intron 1 of MCP-1, and -1385A in the Eotaxin promoter) were nearly always found together on a 31 kb haplotype (H7) containing the three genes. Frequencies of the three variants and the H7 haplotype were significantly elevated (odds ratio, 0.6; P = 0.005-0.01) in uninfected European-Americans repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated blood products. Conclusions Although the extensive linkage disequilibrium precludes positive identification of the causal variant, the results suggest that genetic variation in the H7 region influences susceptibility to HIV-1 infection. Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 or CXCR4, the observed influence on transmission may result from activation of the immune system in response to infection rather than receptor blockage.
TL;DR: It is found that the number of human chromosome 1 fissions in a specific lineage reflects its general rate of genomic evolution, and historic chromosome exchange appears to have been disproportionately clustered in two breakpoint hotspots on the long arm.
Abstract: Developing ordered gene maps from multiple mammalian species coupled with chromosome-painting data provide a powerful resource for resolving the evolutionary history of chromosomes and whole genomes. In this work, we recapitulate the evolutionary history of human chromosome 1 and its homologs in placental mammals, putatively the largest physical unit in the ancestral placental genome. Precise definition of translocation exchange breakpoints in human, carnivore, cetartiodactyl, and rodent-ordered gene maps demonstrate that chromosome breakpoints, previously considered as equivalent, actually represent distinct chromosome positions and exchange events. Multidirectional chromosome painting, using probes from homologs to chromosome 1 in seven mammal species from six orders of placental mammals, confirm the gene-mapping results and indicate that the multiple human chromosome 1 homologs in these species are derived from independent fissions of a single ancestral chromosome. Chromosome painting using human chromosome 1 probes identifies a single human chromosome 1 homolog in phylogenetically distant taxa, the two-toed sloth, cetaceans, and higher primates. The diverse phylogenetic occurrence of a single Hsa1 synteny among the major clades of placental mammals suggests that human chromosome 1 represents an intact ancestral chromosome, which was variously fissioned in the majority of placental species. We find that the number of human chromosome 1 fissions in a specific lineage reflects its general rate of genomic evolution. Further, historic chromosome exchange appears to have been disproportionately clustered in two breakpoint hotspots on the long arm.
TL;DR: This report discusses the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells, and recommends that scientists, policy makers, and the public discuss these issues responsibly.
TL;DR: If stem cells fulfill their therapeutic promise, moving them from the laboratory into the clinic will raise several concerns about justice, and the authors can avoid this outcome by carefully selecting the stem cells they make available.
Abstract: If stem cells fulfill their therapeutic promise, moving them from the laboratory into the clinic will raise several concerns about justice. One concern is that, for biological reasons alone, stem cell-based therapies might not be available for every patient who needs one. Worse, depending on how we address the problem of biological access, they might benefit primarily white Americans. We can avoid this outcome—although at a cost—by carefully selecting the stem cells we make available.
TL;DR: It is suggested that differential preferences for amino acids at the C terminus may influence peptide-binding capacity, and TAP2 Ala665 was associated with resistance to HIV-1 infection, perhaps because of its higher efficiency in transporting peptides, thus eliciting a greater CD8(+) T cell response, or because of linkage disequilibrium.
Abstract: To examine the relationship of human leukocyte antigen (HLA) class I and transporter associated with antigen processing (TAP) genes with resistance to human immunodeficiency virus type 1 (HIV-1) infection, 100 HIVseronegative men who had been exposed repeatedly to HIV-1 were compared with 184 men who had seroconverted to HIV positive and had lower risk. In the univariate analysis, the HLA-A2 supertype, excluding A*0201 (HLAA2/6802 supertype; odds ratio [OR], 4.45; 95% confidence interval [CI], 1.33‐4.84; ) was associated with P p .009 resistance to HIV-1 infection; the effect was the result of the presence of the A*0205 subgroup alleles. Susceptibility was associated in univariate analysis with the B*35 Px alleles (OR, 0.29; 95% CI, 0.08‐0.99; ), which P p .037
TL;DR: These 304 novel polymorphic repeat loci in the feline genome provide a useful tool for undertaking full-genome scans to identify genes associated with phenotypes of interest, such as those relating to hereditary disease, coat color, patterning and morphology.
Abstract: Effective utilization of the domestic cat as an animal model for hereditary and infectious disease requires the development and implementation of high quality gene maps incorporating microsatellites and conserved coding gene markers. Previous feline linkage and radiation hybrid maps have lacked sufficient microsatellite coverage on all chromosomes to make effective use of full genome scans. Here we report the isolation and genomic mapping of 304 novel polymorphic repeat loci in the feline genome. The new loci were mapped in the domestic cat radiation hybrid panel using an automated fluorescent Taq-Man based assay. The addition of these 304 microsatellites brings the total number of microsatellites mapped in the feline genome to 580, and the total number of loci placed onto the RH map to 1,126. Microsatellites now span every autosome with an average spacing of roughly one polymorphic STR every five centimorgans, and full genome coverage of one marker every 2.7 megabases. These loci now provide a useful tool for undertaking full-genome scans to identify genes associated with phenotypes of interest, such as those relating to hereditary disease, coat color, patterning and morphology. These resources can also be extended to the remaining 36 species of the cat family for population genetic and evolutionary genomic analyses.
TL;DR: It is concluded that the LHBT does not play a significant role in either the rotator cuff–deficient or normal shoulder, and an EMG analysis of the LH BT in 10 shoulders supported this finding.
Abstract: found no significant increase in bicepsbrachii activity during isolated shoulder motion when thepatient’s elbow motion was controlled with a brace. Theyconcluded that the LHBT does not play a significant rolein either the rotator cuff–deficient or normal shoulder.Levy et al supported this finding in an EMG analysis ofthe LHBT in 10 shoulders, in which shoulder motion wasisolated by using a long arm brace to lock the elbow inextension and the forearm in the neutral position.
TL;DR: Maximum likelihood, minimum evolution, maximum parsimony, and Bayesian posterior probabilities all provide robust support for the association of Mystacina with the South American noctilionoids.
TL;DR: It is suggested that CXCR6 may play a role in late-stage HIV-1 infection and may alter the progression to death after initial infection with PCP.
Abstract: CXCR6 is a chemokine receptor and the primary coreceptor in SIV infection. A single nucleotide polymorphism 1469G-->A, results in a nonconservative change in codon 3 (CXCR6-E3K) of the N-terminus of the coreceptor. To investigate the relation between the chemokine receptor CXCR6 genotype and progression to Pneumocystis carinii pneumonia (PCP) and from PCP to death, we clinically assessed and genotyped 805 individuals from an African-American injection drug-using cohort in Baltimore, MD, USA, for this CXCR6-E3K polymorphism. The allele frequency of CXCR6-3K was high (44%) in African Americans and rare in European Americans (f<1%). Although time to AIDS and PCP was similar for all CXCR6 genotypes, the median survival time from PCP to death for the CXCR6-3E/E and CXCR6-3E/K genotype was 1.5 years compared to 3.1 years for the CXCR6-K/K genotype. Individuals homozygous or heterozygous for the CXCR6-3E allele were 5.6 times more likely to die a PCP-mediated AIDS-related death than were individuals homozygous for CXCR6-3K. This study shows an association between CXCR6 genotype and progression from PCP to death among African-Americans with HIV. We suggest that CXCR6 may play a role in late-stage HIV-1 infection and may alter the progression to death after initial infection with PCP.
TL;DR: A polymorphism, -179G/T, in the promoter of the interferon (IFN)-gamma gene (IFNG) confers differential tumor necrosis factor-alpha (TNF-alpha) inducibility to the IFNG promoter, suggesting that IFNG -179T is a risk factor for AIDS progression, as measured by CD4 cell count.
Abstract: A polymorphism, -179G/T, in the promoter of the interferon (IFN)-gamma gene (IFNG) confers differential tumor necrosis factor-alpha (TNF-alpha) inducibility to the IFNG promoter. The rarer allele, -179T, but not -179G, is inducible by TNF-alpha. We investigated the effects of IFNG -179G/T on AIDS pathogenesis. In 298 African American human immunodeficiency virus (HIV)-1 seroconverters, the IFNG -179G/T genotype was associated with accelerated progression to CD4 <200 and AIDS-1993, a finding suggesting that IFNG -179T is a risk factor for AIDS progression, as measured by CD4 cell count. It is possible that increased IFN-gamma production induced by TNF-alpha when -179T is present causes CD4 cell depletion by apoptosis.
[...]
TL;DR: Even though the coverage of the dog genome (1.5x) is lower than that of mouse (8x), there are many valuable insights to be gained from comparing the sequence of dog with those of mouse and human.
Abstract: The genomes of human, mouse, and rat have been sequenced. Now, as [O'Brien and Murphy][1] announce in their Perspective, the genome sequence derby is heating up with the addition of dog to the list ([ Kirkness et al .][2]). As they explain, even though the coverage of the dog genome (1.5x) is lower than that of mouse (8x), there are many valuable insights to be gained from comparing the sequence of dog with those of mouse and human.
[1]: http://www.sciencemag.org/cgi/content/full/301/5641/1854
[2]: http://www.sciencemag.org/cgi/content/short/301/5641/1898
TL;DR: Genomic distances between species, dominated by inversions (reversals) and translocations, are presented in a first multispecies attempt using ordered mapping data to reconstruct the evolutionary exchanges that preceded modern placental mammal genomes.
Abstract: Rapidly developing comparative gene maps in selected mammal species are providing an opportunity to reconstruct the genomic architecture of mammalian ancestors and study rearrangements that transformed this ancestral genome into existing mammalian genomes. Here, the recently developed Multiple Genome Rearrangement (MGR) algorithm is applied to human, mouse, cat and cattle comparative maps (with 311-470 shared markers) to impute the ancestral mammalian genome. Reconstructed ancestors consist of 70-100 conserved segments shared across the genomes that have been exchanged by rearrangement events along the ordinal lineages leading to modern species genomes. Genomic distances between species, dominated by inversions (reversals) and translocations, are presented in a first multispecies attempt using ordered mapping data to reconstruct the evolutionary exchanges that preceded modern placental mammal genomes.
TL;DR: Single-strand conformation polymorphism analysis of the second exon of the DQB gene in the endemic New Zealand sea lion was automated using fluorescently-labelled PCR primers and a capillary sequencer and found only two alleles defined by changes at a single codon of this apparently functional locus.
Abstract: Single-strand conformation polymorphism (SSCP) analysis of the second exon of the DQB gene in the endemic New Zealand sea lion (Phocarctos hookeri) was automated using fluorescently-labelled PCR primers and a capillary sequencer. SSCP mobility profiles (n = 61 individuals) were confirmed by direct sequencing of genomic polymerase chain reaction (PCR) products (n = 39). We found only two alleles defined by changes at a single codon of this apparently functional locus. SSCP at a constant temperature above ambient allowed consistent and rapid genotyping. By comparison, sequence-based genotyping was highly dependent on the threshold used to identify secondary peaks indicative of a heterozygote.
TL;DR: The data support the recommendation that quantification of BCR-ABL transcripts is essential for optimum management of CMLpatients who achieve CCyR on imatinib, and show that Q-PCR values in CML patients inCCyR are very variable.
TL;DR: The genetic status and implication for conservation management of the Far Eastern leopard subspecies are discussed and strategies for survival of the leopard in the wild are developed.
TL;DR: Genetic epidemiological analyses were conducted among European American and African American participants enrolled in five USA-based HIV-1/AIDS cohorts and failed to identify any significant associations with HIV- 1 infection or progression to AIDS.
Abstract: Interleukin-4 (IL-4) is a pleiotropic cytokine produced primarily by activated CD4(+) T lymphocytes, mast cells, and basophils. It modulates the functions of a variety of cell types involved with the immune response. This cytokine differentially regulates two major HIV-1 coreceptors and activates viral expression, and is thus a reasonable candidate gene for analyses in HIV-1/AIDS cohort studies. Population genetic variation in five single nucleotide polymorphisms (SNPs) in the 5' region of the IL-4 gene was assessed in five racial groups. Neutrality tests reveal that the populations are evolving in accord with the infinite-sites model. However, coalescent simulations suggest greater haplotype diversity among African Americans than expected. This increased variation is presumably attributable to recombination or gene conversion. Genetic epidemiological analyses were conducted among European American and African American participants enrolled in five USA-based HIV-1/AIDS cohorts. One SNP, -589T, known to influence IL-4 transcription was previously shown to be associated with HIV-1/AIDS in both Japanese and French populations. Present analyses failed to identify any significant associations with HIV-1 infection or progression to AIDS.
TL;DR: Comparison of fludarabine-containing salvage chemotherapy regimens for relapsed/refractory acute myelogenous leukemia with different treatment regimens shows clear trends in survival and quality of life for patients with relapsed or refractory leukemia.
Abstract: Comparison of fludarabine-containing salvage chemotherapy regimens for relapsed/refractory acute myelogenous leukemia
Journal Article•
TL;DR: A quantitative polymerase chain reaction (PCR) assay has been developed for the quantification of genomic DNA extracted from domestic cat samples, which targets highly repetitive genomic short interspersed nuclear elements (SINE).
Abstract: A quantitative polymerase chain reaction (PCR) assay has been developed for the quantification of genomic DNA extracted from domestic cat samples. The assay, which targets highly repetitive genomic short interspersed nuclear elements (SINE), can be performed rapidly and is highly sensitive, detecting as little as 10 fg of feline genomic DNA. The assay was linear over a 10 6 dilution range. We have recently developed a short tandem repeat (STR) multiplex panel for forensic analysis of feline specimens. The SINE assay is an integral part of the forensic typing system. The sensitivity of the assay will enable forensic examiners to determine the likelihood of success of genotyping sample extracts with the STR panel without sacrificing valuable DNA necessary to perform genotyping of samples.
Journal Article•
TL;DR: Since the mother-offspring relationship is known in captive populations, the results could resolve unknown paternities in the Chengdu ex situ populations, however, to establish accurately the genetic relationships of wild giant pandas, more microsatellite loci may be required.
Abstract: We used genotype data across 18 microsatellite loci to establish the paternity of giant panda cubs at the Chengdu Zoo and the Chengdu Research Base of Giant Panda Breeding. The results demonstrate that the combined exclusion probability using these 18 microsatellite loci is 0.999921 while confidence is 95 % when the mother is known; if mother is unknown then the exclusion probability is 0.994109, but the confidence of this is less than 80%. Since the mother-offspring relationship is known in captive populations, the results could resolve unknown paternities in the Chengdu ex situ populations. However, to establish accurately the genetic relationships of wild giant pandas,more microsatellite loci may be required.