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Showing papers by "William J. Murphy published in 2009"


Journal ArticleDOI
TL;DR: A precipitous drop in costs and increase in sequencing efficiency is anticipated, with concomitant development of improved annotation technology, and it is proposed to create a collection of tissue and DNA specimens for 10,000 vertebrate species specifically designated for whole-genome sequencing in the very near future.
Abstract: American Genetic Association, Gordon and Betty Moore Foundation, NHGRI Intramural Sequencing Center, and UCSC Alumni Association to cost of the Genome 10K workshop; Howard Hughes Medical Institute to D. H.; Gordon and Betty Moore Foundation to S. C. S.; A

545 citations


Journal ArticleDOI
TL;DR: The molecular decay of ENAM parallels the morphological degeneration of enamel in the fossil record of placental mammals and provides manifest evidence for the predictive power of Darwin's theory.
Abstract: Vestigial structures occur at both the anatomical and molecular levels, but studies documenting the co-occurrence of morphological degeneration in the fossil record and molecular decay in the genome are rare. Here, we use morphology, the fossil record, and phylogenetics to predict the occurrence of “molecular fossils” of the enamelin (ENAM) gene in four different orders of placental mammals (Tubulidentata, Pholidota, Cetacea, Xenarthra) with toothless and/or enamelless taxa. Our results support the “molecular fossil” hypothesis and demonstrate the occurrence of frameshift mutations and/or stop codons in all toothless and enamelless taxa. We then use a novel method based on selection intensity estimates for codons (ω) to calculate the timing of iterated enamel loss in the fossil record of aardvarks and pangolins, and further show that the molecular evolutionary history of ENAM predicts the occurrence of enamel in basal representatives of Xenarthra (sloths, anteaters, armadillos) even though frameshift mutations are ubiquitous in ENAM sequences of living xenarthrans. The molecular decay of ENAM parallels the morphological degeneration of enamel in the fossil record of placental mammals and provides manifest evidence for the predictive power of Darwin's theory.

134 citations


Journal ArticleDOI
TL;DR: The first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936 are reported, adding to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes.
Abstract: We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position within australidelphian marsupials has long been debated, and here we provide strong support for the thylacine's basal position in Dasyuromorphia, aided by mitochondrial genome sequence that we generated from the extant numbat (Myrmecobius fasciatus). Surprisingly, both of our thylacine sequences differ by 11%-15% from putative thylacine mitochondrial genes in GenBank, with one of our samples originating from a direct offspring of the previously sequenced individual. Our data sample each mitochondrial nucleotide an average of 50 times, thereby providing the first high-fidelity reference sequence for thylacine population genetics. Our two sequences differ in only five nucleotides out of 15,452, hinting at a very low genetic diversity shortly before extinction. Despite the samples' heavy contamination with bacterial and human DNA and their temperate storage history, we estimate that as much as one-third of the total DNA in each sample is from the thylacine. The microbial content of the two thylacine samples was subjected to metagenomic analysis, and showed striking differences between a wild-captured individual and a born-in-captivity one. This study therefore adds to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes.

117 citations


Journal ArticleDOI
01 Apr 2009-Genomics
TL;DR: A high-resolution radiation hybrid map of the domestic cat genome is described, which includes 2662 markers, translating to an estimated average intermarker distance of 939 kilobases, and constitutes a comprehensive framework for identifying genes controlling feline phenotypes of interest, and to aid in assembly of a higher coverage feline genome sequence.

48 citations


Journal ArticleDOI
TL;DR: The results indicate that the NF‐κB pathway is a critical regulator of alloresponses and provide a novel small molecule inhibitor based approach that is effective in preventing early posttransplant GVHD lethality but that also permits donor T‐cell responses to recover after a period of lymphopenic expansion.

15 citations


Journal ArticleDOI
TL;DR: The greater phylogeographic range of Epiplatys is hypothesized to be due to retention of ancestral morphology related to a greater adaptability compared to the other five genera.

14 citations


Book ChapterDOI
01 Jan 2009
TL;DR: The role of CD40 stimulation in the generation of innate and adaptive antitumor responses, as well as the direct effects ofCD40 stimulation on tumor survival, death, and angiogenesis are focused on.
Abstract: CD40–CD40L interactions play an important role in the generation of humoral and cell-mediated immunity. Due to the expression of CD40 on antigen presenting cells, it has become an attractive target for immunotherapy against cancer. Recent studies have focused on using CD40 stimulation as an adjuvant, and in conjunction with cytokines and other factors to elicit antitumor responses. However, due to the pleiotropic effects of CD40 stimulation, and the wide array of cell types upon which it is expressed, new studies are also focusing on the nonimmune related consequences of systemic and local CD40 stimulation. Systemic administration of immunotherapy regimens containing CD40 stimulation via soluble ligands and agonist antibodies has been associated with some toxicities, and direct stimulation of CD40 expressed on various malignancies and vascular endothelium has elucidated a possible role for CD40 in the transformation and progression of malignancies. This review focuses on the role of CD40 stimulation in the generation of innate and adaptive antitumor responses, as well as the direct effects of CD40 stimulation on tumor survival, death, and angiogenesis.