Showing papers by "Stephen J. O'Brien published in 1987"
TL;DR: A gene was identified that is amplified more than 50-fold in a malignant glioma, a member of a select group of cellular genes that are genetically altered in primary human tumors.
Abstract: A gene, termed gli, was identified that is amplified more than 50-fold in a malignant glioma. The gene is expressed at high levels in the original tumor and its derived cell line and is located at chromosome 12 position (q13 to q14.3). The gli gene is a member of a select group of cellular genes that are genetically altered in primary human tumors.
669 citations
TL;DR: In an examination of three distinct lion populations, a direct correlation was observed between genetic variability and two physiological traits, incidence of abnormal sperm and circulating testosterone, a critical hormone for spermatogenesis.
Abstract: Species survival is critically dependent on reproductive performance, a complex physiological process under rigorous genetic control. Classical studies of inbreeding in laboratory animals and livestock have shown that increased homozygosity can adversely affect spermatogenesis, ovulation and perinatal mortality and morbidity1–3. For wild populations, the consequences of inbreeding depression have not been examined intensively, although our recent studies of the African cheetah revealed a striking degree of genetic uniformity4,5 combined with an extremely high incidence of structurally abnormal spermatozoa (>70%) in captive6 as well as free-ranging7 males. In this study, we report definitive evidence that the reproductive function of free-ranging mammals can be impaired as a result of demographic contraction followed by inbreeding. In an examination of three distinct lion populations (two from the Serengeti ecosystem in East Africa and a third descended from lions in the Gir Forest of western India), a direct correlation was observed between genetic variability and two physiological traits, incidence of abnormal sperm and circulating testosterone, a critical hormone for spermatogenesis.
376 citations
TL;DR: It is proposed that at least two population bottlenecks followed by inbreeding produced the modern cheetah species.
Abstract: A combined population genetic and reproductive analysis was undertaken to compare free-ranging cheetahs from east Africa (Acinonyx jubatus raineyi) with the genetically impoverished and reproductively impaired south African subspecies (Acinonyx jubatus jubatus). Like that of their south African counterparts, the quality of semen specimens from east African cheetahs was poor, with a low concentration of spermatozoa (25.3 X 10(6) per ejaculate) and a high incidence of morphological abnormalities (79%). From an electrophoretic survey of the products of 49 genetic loci in A. jubatus raineyi, two allozyme polymorphisms were detected; one of these, for a nonspecific esterase, shows an allele that is rare (less than 1% incidence) in south African specimens. Estimates of polymorphism (2-4%) and average heterozygosity (0.0004-0.014) affirm the cheetah as the least genetically variable felid species. The genetic distance between south and east African cheetahs was low (0.004), suggesting that the development of genetic uniformity preceded the recent geographic isolation of the subspecies. We propose that at least two population bottlenecks followed by inbreeding produced the modern cheetah species. The first and most extreme was ancient, possibly late Pleistocene (circa 10,000 years ago); the second was more recent (within the last century) and led to the south African populations.
181 citations
TL;DR: The incidence, basic pathophysiology, and clinical and radiologic examination in posterior instability of the shoulder are discussed in this article, and conservative treatment protocols and surgical procedures are presented.
154 citations
TL;DR: Findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q-chromosome suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).
Abstract: The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, we localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33 [del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent form the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF (the gene encoding granulocyte-macrophage-CSF), CSF-1 (the gene encoding macrophage-CSF), and FMS (the human c-fms protooncogene, which encodes the CSF-1 receptor). Our findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q-chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).
146 citations
TL;DR: The observation of viral-cell transcripts and chromosomal deletions associated with HPV integration may indicate that such events are part of a multistep mechanism leading to the development of cervical cancer.
141 citations
TL;DR: The data indicate that the comparatively poor reproductive performance of cheetahs maintained in zoological parks is not attributable to a captivity-induced response afflicting the male, and suggests that spermatozoal diversity originates as a result of the extreme genetic monomorphism observed universally in the species.
Abstract: Ejaculate-endocrine characteristics were measured in 23 captive cheetahs (Acinonyx jubatus jubatus) in North American zoos and in 8 free-ranging cheetahs (A. j. raineyi) in eastern Africa (Tanzania). A standardized electroejaculation protocol was used, and numbers of motile spermatozoa were similar (p>O.05) between groups. Of the spermatozoa collected by electroejaculation, 70.6 ± 3.3% and 75.9 ± 4.4% were morphologically abnormal in the captive “North American” and in the free-ranging, eastern African populations, respectively. Adrenal activity, as measured by an acute, temporal rise and fall in serum cortisol levels during and after electroejaculation, was no different (p> 0.05) between groups. Although serum luteinizing hormone (LH) levels were less (p< 0.05) In the free-ranging than in the captive animals, serum testosterone concentrations were similar. The data indicate that the comparatively poor reproductive performance of cheetahs maintained in zoological parks is not attributable to a captivity-induced response afflicting the male. Furthermore, there is no evidence that ejaculate/endocrine characteristics differ between the two subspecies. Because adrenal /gonadal activity and the number of pleiomorphic spermatozoa are similar between the test groups, the results suggest that spermatozoal diversity originates as a result of the extreme genetic monomorphism observed universally in the species.
116 citations
TL;DR: To successfully treat anterior shoulder instability, surgeons should address the labrum, chondral surfaces, and bony fractures and defects.
114 citations
TL;DR: The results suggest that the blade-like trenchant heel on the carnassial tooth has evolved indepen- dently at least twice within the Canidae, and several distinct genetic stocks appear to have led to the extant South American canids.
Abstract: Protein products of 51 genetic loci were analyzed by gel electrophoresis using extracts of blood and tissue culture specimens from 12 of the 14 extant canid genera. Genetic distances were calculated and used to derive phenetic trees. The results suggest that the Canidae can be divided into several distinct groups. The wolf-like canids are a group that includes species in the genus Canis and Lycaon pictus (African wild dog). Speothos venaticus (Brazilian bush dog) is weakly associated with this group. Based on the calibration of a consensus tree with a fossil date, Canis mesomelas (black-backed jackal) and Speothos venaticus separated first, approximately 6 million years before present (MYBP). Lycaon pictus and C. latrans (coyote) separated from the line leading to C. lupus (grey wolf) and C. familiaris (domestic dog) approximately 3 MYBP. These results suggest that the blade-like trenchant heel on the carnassial tooth has evolved indepen- dently at least twice within the Canidae. Several distinct genetic stocks appear to have led to the extant South American canids. Chrys- ocyon brachyurus (maned wolf) is estimated to have diverged from Dusicyon vetulus (hoary fox) and Cerdocyon thous (crab-eating fox) approximately 6 MYBP. The divergence time of the last two genera is fairly recent (2-3 MYBP) and is coincident with the opening of the Panamanian land bridge. The remaining South American canid included in this survey, Speothos venaticus, is clustered with the wolf-like canids. The Vulpes-like canids are a distinct phenetic group that includes species in the genera Vulpes, Alopex and Fennecus. Their estimated time of divergence from all the other canids, approximately 9 MYBP, is among the oldest within the Canidae. Among the Vulpes-like canids we surveyed, Alopex lagopus (arctic fox) and Vulpes macrotis (kit fox) appear genetically most closely related. Finally, the biochemical data support the generic status of three canid genera: Urocyon, Nyctereutes, and Otocyon. These taxa are not closely related to any of the surveyed canid species. (Allozyme; electrophoresis; phenogram; Canidae; evolution; trenchant heel; South America.)
99 citations
TL;DR: The results suggest that the South American canids are closely related to each other and are derived from awolf-like progenitor, and the fennec and the bat-eared fox seem to be recent derivatives of a lineage that branched early from the wolf-like canids.
Abstract: The Giemsa banding patterns of seven canid species, including the grey wolf (Canis lupus), the maned wolf (Chrysocyon brachyurus), the bush dog (Speothos venaticus), the crab-eating fox (Cerdocyon thous), the grey fox (Urocyon cinereoargenteus), the bat-eared fox (Otocyon megalotis), and the fennec (Fennecus zerda), are presented and compared. Relative to other members of Canidae, these species have high diploid complements (2n greater than 64) consisting of largely acrocentric chromosomes. They show a considerable degree of chromosome homoeology, but relative to the grey wolf, each species is either missing chromosomes or has unique chromosomal additions and rearrangements. Differences in chromosome morphology among the seven species were used to reconstruct their phylogenetic history. The results suggest that the South American canids are closely related to each other and are derived from a wolf-like progenitor. The fennec and the bat-eared fox seem to be recent derivatives of a lineage that branched early from the wolf-like canids and which also includes the grey fox.
92 citations
TL;DR: A molecular phylogeny for the hominoid primates was constructed by using genetic distances from a survey of 383 radiolabeled fibroblast polypeptides resolved by two-dimensional electrophoresis (2DE), appearing to resolve the human-chimpanzee-gorilla trichotomy in favor of a more recent association of chimpanzees and humans.
Abstract: A molecular phylogeny for the hominoid primates was constructed by using genetic distances from a survey of 383 radiolabeled fibroblast polypeptides resolved by two-dimensional electrophoresis (2DE). An internally consistent matrix of Nei genetic distances was generated on the basis of variants in electrophoretic position. The derived phylogenetic tree indicated a branching sequence, from oldest to most recent, of cercopithecoids (Macaca fascicularis), gibbon-siamang, orangutan, gorilla, and human-chimpanzee. A cladistic analysis of 240 electrophoretic characters that varied between ape species produced an identical tree. Genetic distance measures obtained by 2DE are largely consistent with those generated by other molecular procedures. In addition, the 2DE data set appears to resolve the human-chimpanzee-gorilla trichotomy in favor of a more recent association of chimpanzees and humans.
TL;DR: The history of chromosomal rearrangements within the Canidae family is presented based on the assumption that a metacentric-dominated karyotype is primitive for the group.
Abstract: The Giemsa-banding patterns of chromosomes from the arctic fox (Alopex lagopus), the red fox (Vulpes vulpes), the kit fox (Vulpes macrotis), and the raccoon dog (Nyctereutes procyonoides) are compared. Despite their traditional placement in different genera, the arctic fox and the kit fox have an identical chromosome morphology and G-banding pattern. The red fox has extensive chromosome arm homoeology with these two species, but has only two entire chromosomes in common. All three species share some chromosomes with the raccoon dog, as does the high diploid-numbered grey wolf (Canis lupus, 2n = 78). Moreover, some chromosomes of the raccoon dog show partial or complete homoeology with metacentric feline chromosomes which suggests that these are primitive canid chromosomes. We present the history of chromosomal rearrangements within the Canidae family based on the assumption that a metacentric-dominated karyotype is primitive for the group.
TL;DR: A comprehensive analysis of the homologous banding patterns within the Ursidae and with a hypothesized ancestral carnivore karyotype permitted the reconstruction of three significant chromosomal reorganization events that occurred during the evolution of the modern ursids.
Abstract: Trypsin G-banded karyotypes of eight species of Ursidae were prepared from retrovirus-transformed skin fibroblast cultures. The banding patterns of all bears are highly conserved, even though their diploid numbers range from 42 to 72. A comprehensive analysis of the homologous banding patterns within the Ursidae and with a hypothesized ancestral carnivore karyotype permitted the reconstruction of three significant chromosomal reorganization events that occurred during the evolution of the modern ursids. The first was a multichromosomal fissioning away from the biarmed (2n = 44) primitive carnivore karyotype, leading to six species of the Ursinae subfamily (2n = 78). The second was a comprehensive chromosome fusion in the lineage that led to the Ailuropodinae (giant panda) subfamily (2n = 44). The third event was a second, independent, but less extensive, centromeric fusion occurring in the line that led to the Tremarctinae (spectacled bear) subfamily (2n = 52). Ursidae karyotypes are not only highly conserved within the family but also exhibit extensive chromosome banding homology with other carnivore families.
TL;DR: The detailed methods employed in the laboratory for gene mapping and cytogenetic analyses in human beings, in the domestic cat, and in other mammalian species are presented.
TL;DR: Pedigree analysis of the genetic transmission of these three biochemical loci demonstrated that two of the five primary founder animals of the SSP Asiatic lion population were descendants of the African subspecies.
Abstract: The Asiatic lion (Panthera leo persica) exists in the wild as a single relict population of approximately 250 individuals in the protected Gir Forest Sanctuary in western India. In 1981, a species survival plan (SSP) for the Asiatic lion was established by the American Association of Zoological Parks and Aquariums to manage the 200 + descendants of Asiatic lions in captivity in western zoological facilities. This captive population was derived from seven founders. In order to compare the genetic structure of the Gir Forest population with that of the captive SSP population, a genetic survey of 46 electrophoretic allozyme systems resolved from extracts of lion blood was undertaken by using 29 SSP Asiatic lions and 28 wild-caught or captive-bred lions maintained at the Sakkarbaug Zoo in India but originally derived from the Gir Forest. The Gir lion population was found to be genetically monomorphic at each of 46 allozyme loci. This was in contrast to several African lion (Panthera leo leo) populations, which show moderate levels of allozyme variation at the same loci. The SSP lion population was polymorphic at three allozyme loci (IDHI, TF, and PTI) for alleles that were previously found only in African lion populations. Pedigree analysis of the genetic transmission of these three biochemical loci demonstrated that two of the five primary founder animals of the SSP Asiatic lion population (a breeding pair originally imported from the Trivandrum Zoo in southern India) were descendants of the African subspecies. Three other founder animals were pure Asian. A retrospective SSP pedigree analysis of two morphologic characters (prominent abdominal fold and pairing of infraorbital foramen) that are partially diagnostic for persica vs leo was consistent with this conclusion as well. The implications for the management of small captive populations of threatened species and of the Asiatic lion SSP population are discussed.
Journal Article•
TL;DR: With a human myelin-basic-protein (MBP) cDNA used as a probe, the human MBP gene has been mapped to chromosome region 18q22-q23 by a combination of Southern hybridization to a panel of somatic-cell hybrid DNAs and in situ hybridized to metaphase chromosomes.
Abstract: With a human myelin-basic-protein (MBP) cDNA used as a probe, the human MBP gene has been mapped to chromosome region 18q22-q23 by a combination of Southern hybridization to a panel of somatic-cell hybrid DNAs and in situ hybridization to metaphase chromosomes Restriction-fragment-length polymorphisms (RFLPs) have also been identified with this probe in human DNA, by means of the restriction enzymes BamHI, PvuII, and PstI In studies of informative families, the alleles of the BamHI and PvuII polymorphisms have been shown to segregate as Mendelian traits
TL;DR: A new family of moderately repetitive DNA sequences, unique because of its organization in clustered tandem arrays, its length, its chromosomal location, and its lack of homology to other moderately repetitive sequence families is identified.
Abstract: In cloning adenovirus homologous sequences, from a human cosmid library, we identified a moderately repetitive DNA sequence family consisting of tandem arrays of 2.5 kb members. A member was sequenced and several non-adjacent, 15-20 bp G-C rich segments with homology to the left side of adenovirus were discovered. The copy number of 400 members is highly conserved among humans. Southern blots of partial digests of human DNA have verified the tandem array of the sequence family. The chromosomal location was defined by somatic cell genetics and in situ hybridization. Tandem arrays are found only on chromosomes 4 (4q31) and 19 (q13.1-q13.5). Homologous repetitive sequences are found in DNA of other primates but not in cat or mouse. Thus we have identified a new family of moderately repetitive DNA sequences, unique because of its organization in clustered tandem arrays, its length, its chromosomal location, and its lack of homology to other moderately repetitive sequence families.
TL;DR: The presence of the genes for type IV collagen chains on chromosome 13 excludes a primary role for these genes in adult polycystic kidney disease and X-linked forms of hereditary nephritis.
Abstract: We have isolated a 2.1-kb cDNA clone from a human placental library encoding part of the α2 chain of collagen IV, a major structural protein of basement membranes. The DNA sequence encodes 446 amino acids in the triplehelical domain plus the 227 amino acids of the carboxy-terminal globular domain. The latter structure is composed of two homologous subdomains and is highly conserved between the α1 and α2 chains. The triple-helical domain contained seven interruptions of the Gly-X-Y repeat and these interruptions were in general larger than their counterparts in the α1 chain. DNA from human rodent hybrid cell lines was analyzed under conditions in which there was no cross-hybridization of the α2(IV) cDNA probe with the gene for the α1(IV) collagen chain. An Eco RI fragment characteristic of the α2 chain had a concordance of 0.97 with chromosome 13. This result was confirmed and extended with in situ localization of the gene at 13q34. Since the α1(IV) gene has previously been localized to 13q34, the two type IV collagen genes reside in the same chromosome region (13q34), possibly in a gene cluster. The presence of the genes for type IV collagen chains on chromosome 13 excludes a primary role for these genes in adult polycystic kidney disease and X-linked forms of hereditary nephritis.
TL;DR: The close linkage of met to the gene responsible for cystic fibrosis in humans suggests that further genetic analysis of mouse chromosome 6 may be useful in developing a mouse model for the disease.
TL;DR: Brain structure and correlation patterns in Insectivora, Chiroptera, and Primates, and Brain structure and correlations in insects andPrimates, 1975.
Abstract: ation in the wolf, Canis lupus L. Evolution 13:283299. ---. 1984. Principal components, factor analysis, and multivariate allometry: A small-sample direction test. Biometrics 40:685-690. JOLICOEUR, P., P. PIRWT, G. BARON, AND H. STEPHAN. 1984. Brain structure and correlation patterns in Insectivora, Chiroptera, and Primates. Syst. Zool. 33:14-29. KRAMER, C. Y. 1972. A First Course in Methods of Multivariate Analysis. Kramer, Blackburg, VA. NIE, N. H., C. H. HULL, J. G. JENKINS, K. STEINBRENNER, AND D. H. BENT. 1975. SPSS: Statistical Package for the Social Sciences. McGraw-Hill, N.Y.
Journal Article•
TL;DR: A cDNA clone encoding the B1 chain of human laminin has been isolated from a human endothelial cell cDNA library using a panel of rodent/human somatic-cell hybrids and in situ hybridization.
Abstract: A cDNA clone encoding the B1 chain of human laminin has been isolated from a human endothelial cell cDNA library. With use of this probe and a panel of rodent/human somatic-cell hybrids and in situ hybridization, the gene for the human laminin-B1 chain has been localized to chromosome 7, band q31.
Journal Article•