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Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 289 records · Page 16Linked to original sources
PubMed1997

Mutational analysis and expression studies of the neurofibromatosis type 2 (NF2) gene in a patient with a ring chromosome 22 and NF2.

The case of a seriously disabled and retarded female patient with neurofibromatosis type 2 (NF2) is reported. She suffered from bilateral vestibular schwannomas, multiple intracranial meningiomas and neurinomas. The constitutional karyotype of the patient was 46, XX, r(22)/45,XX,-22. A constitutional G to A transition in the proximal 3' untranslated region of isoforms 1 and 2 was identified in the patient's NF2 gene and shown not to affect differential splicing or mRNA stability. The instability of the ring chromosome 22 with the associated loss of tumor suppressor genes on chromosome 22, in particular the loss of the NF2 gene, are assumed to have caused multiple tumorigenesis in this patient.

Adult↗
PubMed1997

Cerivastatin: pharmacology of a novel synthetic and highly active HMG-CoA reductase inhibitor.

The pyridine derivative cerivastatin is a new entirely synthetic and enantiomerically pure inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. As a sodium salt cerivastatin is present in the active, open ring form. Cerivastatin inhibited the membrane-bound (non-solubilized) HMG-CoA reductase of the native microsomal fraction isolated from rat liver with a Ki value of 1.3 x 10(-9) M. The reference compound lovastatin was 100-fold less potent and exhibited a Ki value of 150 x 10(-9) M. Cerivastatin inhibited the cholesterol synthesis in the human hepatoma cell line HepG2 cells with a similar IC50 value of 1.0 x 10(-9) M. In vivo studies reflected its high in vitro activity. In both rats and dogs, cerivastatin inhibited the hepatic [14C]cholesterol synthesis from [14C]acetate with an oral ED50 value of 0.002 mg/kg body weight, while lovastatin exhibited an oral ED50 value of 0.3 mg/kg in rats, showing again the ratio of 100 or more between cerivastatin and lovastatin. In the small intestine and testes, cerivastatin was at least 50-fold less active with oral ED50 values higher than 0.1 mg/kg, which is indicative for a high liver selectivity of cerivastatin. In cholestyramine-primed dogs cerivastatin dose-dependently lowered the serum cholesterol concentrations by up to 59% with 0.1 mg/kg after 20 days. Interestingly, the serum triglycerides were markedly reduced by 53 and 76% with 0.03 and 0.1 mg/kg, respectively. In normal chow fed dogs the low density lipoprotein (LDL) concentrations were reduced by up to 75% after 0.1 mg cerivastatin/kg. The ratio of HDL/LDL increased by 81% compared with a change of only 14% in the placebo treated control group. The antiatherogenic effect of cerivastatin was shown in rabbits fed a diet enriched with 0.2% cholesterol. After 9 weeks on diet 0.1 mg cerivastatin/kg decreased the accumulation of cholesterol ester in the arterial tissue by 73%. In summary, these data as compared to published data on other HMG-CoA reductase inhibitors demonstrate cerivastatin to be the most active compound in this class. Vastatins used in therapy are effective in mg doses, while cerivastatin offers a new low dose therapy in the microg range.

Administration, Oral↗
PubMed1997

Multiple chromosomal mechanisms generate an EWS/FLI1 or an EWS/ERG fusion gene in Ewing tumors.

The t(11;22)(q24;q12) translocation is found in about 85% of Ewing tumors and leads in all cases to an EWS/FLI1 fusion gene. In a few instances, complex translocations, involving chromosomes 11, 22 and a third chromosome or other variant translocations not involving chromosome 11 also have been reported. These rearrangements generate an active fusion gene between the EWS gene and either the human FLI1 gene or other members of the ETS gene family: the ERG gene localized in band 21q22.2, the ETV1 gene localized in band 7p22, or the E1AF gene localized in band 17q12. Using fluorescence in situ hybridization (FISH) on interphase nuclei or metaphases, we report here the characterization of particular karyotypes in Ewing tumors, namely a complex t(2;11;22) translocation, a variant t(12;22) translocation, and one Ewing tumor without specific rearrangements but with an EWS/ERG fusion gene demonstrated by molecular analysis. These molecular cytogenetic methods allowed us (1) to precisely localize the genomic breakpoints within-EWSR1 and EWSR2 and to identify the chromosome carrying the fusion gene; (2) to determine the nature of events generating the fusion genes; (3) to demonstrate that some variant translocations represent masked complex translocations; and (4) to show that the generation of an EWS/ERG fusion gene cannot be obtained through a simple balanced translocation.

Chromosome Aberrations↗
PubMed1997

TOR signalling and control of cell growth.

TOR, phosphatidylinositol 3-kinase, p70s6k, and 4E-BP1 have recently emerged as components of a major signalling pathway that is dedicated to protein translation and thus to cell growth. This pathway appears to be conserved, at least in part, in yeast, slime molds, plants, flies, and mammals. TOR and phosphatidylinositol 3-kinase control p70s6k and 4E-BP1, which, in turn, directly control the translation initiation machinery.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Infrequent microsatellite instability in oesophageal cancers.

Alterations of microsatellites have been found at relatively high frequency in hereditary and sporadic colorectal cancer and gastric and pancreatic cancers and at lower frequency in some other cancers. We determined the frequency of instability at 39 poly-CA microsatellite loci in 20 squamous cell carcinomas and 26 Barrett's adenocarcinomas of the oesophagus. None of the tumours presented instability for a high percentage of the tested loci. Four squamous cell carcinomas and six Barrett's adenocarcinomas showed microsatellite instability at one locus, and three Barrett's adenocarcinomas showed microsatellite instability at two loci. The presence of few loci showing microsatellite instability could be due to an instability background. We conclude that genetic defects in the DNA mismatch repair system do not play an important role in oesophageal cancers.

Adenocarcinoma↗
PubMed1997

20 Years of Progress in Radiation Oncology: Prostate Cancer.

Carcinoma of the cervix remains of special interest to the Patterns of Care Study (PCS) because of the prominent role that radiotherapy plays in the definitive management of all stages and extents of disease. Five PCS surveys have been conducted for squamous cell cancer of the uterine cervix beginning in 1973 and repeated thereafter at 5-year intervals. The records of over 2,700 women have been reviewed for these surveys. Changes in the pretreatment investigations of cervical cancer patients have occurred during these years, with an increase in the use of computed tomography (CT) and a decrease in the use of intravenous pyelography and cystoscopy. A marked increase in the use of linear accelerators has also occurred, with 98% of all facilities having a linear accelerator as the highest energy treatment machine in the 1988 survey. There has been a change in brachytherapy prescription over the time of the surveys, with most institutions reporting point dose calculations and dose distributions instead of milligram hours. Mean point A dose has increased to approximately 80cGy, reflecting the PCS recommendations of dose intensity to the paracentral point through use of brachytherapy. The outcome for stage I and II cervical cancer has remained stable over the time of the surveys, while the results have improved for stage III disease. This improvement in survival and local control for stage III cervical cancer is due in part to the PCS, which has developed standards of treatment with the goal of radiation dose intensity. A number of patient, tumor, and treatment factors significant in multivariate analysis have been described by the PCS with large cohorts of patients. The most important treatment factors associated with a decrease in pelvic failure and improved survival are the use of brachytherapy and higher paracentral dose. A significant dose response has been described for stage III cervical cancer and optimal pelvic control has been demonstrated with point A doses above 8,500 cGy. Other treatment factors associated with improved outcome include the reduction of overall treatment time, particularly for stage III cervical cancer, and the adequacy of an intracavitary placement. The rate and time course of major complications associated with the radiation for cervix cancer has been described by the PCS. An increase in complications was seen for young patients and those with a history of abdominal surgery. Treatment factors that increased the risk of complications included a fraction size greater than 7,500 cGy, and the use of staging laparotomy via a transperitoneal approach. Through the findings of the PCS, national averages of the process and outcome of radiation for cervical cancer as well as the important patient, tumor, and treatment factors that affect outcome have been reported. These results have positively affected routine clinical practice. Greater emphasis is placed on the use of intracavitary radiation therapy (RT) and dose escalation, as well as on a reduction in overall treatment time for cervical cancer. Future research will focus on the use of new technologies, such as high-dose rate brachytherapy and the impact of CT- and magnetic resonance imaging-directed treatment planning on local tumor control and survival. It will specifically evaluate the radiation treatment and outcome of minority populations. It will also measure the adoption of the results of positive clinical trials and the findings from previous PCS analyses into the national practice of radiation oncology.

Journal Article↗
PubMed1997

An instrumented glove for grasp specification in virtual-reality-based point-and-direct telerobotics.

Hand posture and force, which define aspects of the way an object is grasped, are features of robotic manipulation. A means for specifying these grasping "flavors" has been developed that uses an instrumented glove equipped with joint and force sensors. The new grasp specification system will be used at the Pennsylvania State University (Penn State) in a Virtual Reality based Point-and-Direct (VR-PAD) robotics implementation. Here, an operator gives directives to a robot in the same natural way that human may direct another. Phrases such as "put that there" cause the robot to define a grasping strategy and motion strategy to complete the task on its own. In the VR-PAD concept, pointing is done using virtual tools such that an operator can appear to graphically grasp real items in live video. Rather than requiring full duplication of forces and kinesthetic movement throughout a task as is required in manual telemanipulation, hand posture and force are now specified only once. The grasp parameters then become object flavors. The robot maintains the specified force and hand posture flavors for an object throughout the task in handling the real workpiece or item of interest. In the Computer integrated Manufacturing (CIM) Laboratory at Penn State, hand posture and force data were collected for manipulating bricks and other items that require varying amounts of force at multiple pressure points. The feasibility of measuring desired grasp characteristics was demonstrated for a modified Cyberglove impregnated with Force-Sensitive Resistor (FSR) (pressure sensors in the fingertips. A joint/force model relating the parameters of finger articulation and pressure to various lifting tasks was validated for the instrumented "wired" glove. Operators using such a modified glove may ultimately be able to configure robot grasping tasks in environments involving hazardous waste remediation, flexible manufacturing, space operations and other flexible robotics applications. In each case, the VR-PAD approach will finesse the computational and delay problems of real-time multiple-degree-of-freedom force feedback telemanipulation.

Biomechanical Phenomena↗
PubMed1997

Summer mastitis experimentally induced by Hydrotaea irritans exposed to bacteria.

Summer mastitis is an acute suppurative bacterial infection of the udder in heifers and dry cows. To ascertain the possible role of flies in the transmission of the disease, experimental exposures of recipient heifers to Hydrotaea irritans previously exposed to bacteria were carried out. Flies were allowed to feed on secretions from clinical cases of summer mastitis. The pathogens present were the bacteria Staphylococcus aureus, Streptococcus dysgalactiae, Actinomyces pyogenes, Stuart-Schwan cocci, Peptococcus indolicus, Fusobacterium necrophorum and Bacterioides species. The teats of eight heifers were exposed to flies with verified pathogen content. Two teats of each animal were deliberately damaged before fly exposure. One teat was cut, another pricked with insect needles to mimic insect bites. Two of the heifers developed summer mastitis in the quarters where teats had been cut. The bacterial species isolated from these quarters corresponded to those that had previously been fed to the flies. For the first time, it is now demonstrated that H.irritans is capable of transmitting summer mastitis pathogens and so causing summer mastitis in recipient heifers. Lesions on the teat orifice may be a predisposing factor in the development of the disease.

Animals↗
PubMed1997

The insulin-induced signalling pathway leading to S6 and initiation factor 4E binding protein 1 phosphorylation bifurcates at a rapamycin-sensitive point immediately upstream of p70s6k.

Employing specific inhibitors and docking-site mutants of growth factor receptors, recent studies have indicated that the insulin-induced increase in 40S ribosomal protein S6 and initiation factor 4E binding protein 1 (4E-BP1) phosphorylation is mediated by the mTOR/FRAP-p70s6k signal transduction pathway. However, it has not been resolved whether the phosphorylation of both proteins is mediated by p70s6k or whether they reside on parallel pathways which bifurcate upstream of p70s6k. Here we have used either rapamycin-resistant, kinase-dead, or wild-type p70s6k variants to distinguish between these possibilities. The rapamycin-resistant p70s6k, which has high constitutive activity, was able to signal to S6 in the absence of insulin and to prevent the rapamycin-induced block of S6 phosphorylation. This same construct did not increase the basal state of 4E-BP1 phosphorylation or protect it from the rapamycin-induced block in phosphorylation. Unexpectedly, the rapamycin-resistant p70s6k inhibited insulin-induced 4E-BP1 phosphorylation in a dose-dependent manner. This effect was mimicked by the kinase-dead and wild-type p70s6k constructs, which also blocked insulin-induced dissociation of 4E-BP1 from initiation factor 4E. Both the kinase-dead and wild-type constructs also blocked reporter p70s6k activation, although only the kinase-dead p70s6k had a dominant-interfering effect on S6 phosphorylation. Analysis of phosphopeptides from reporter 4E-BP1 and p70s6k revealed that the kinase-dead p70s6k affected the same subset of sites as rapamycin in both proteins. The results demonstrate, for the first time, that activated p70s6k mediates increased S6 phosphorylation in vivo. Furthermore, they show that increased 4E-BP1 phosphorylation is controlled by a parallel signalling pathway that bifurcates immediately upstream of p70s6k, with the two pathways sharing a common rapamycin-sensitive activator.

Carrier Proteins↗
PubMed1997

Dual requirement for a newly identified phosphorylation site in p70s6k.

The activation of p70s6k is associated with multiple phosphorylations at two sets of sites. The first set, S411, S418, T421, and S424, reside within the autoinhibitory domain, and each contains a hydrophobic residue at -2 and a proline at +1. The second set of sites, T229 (in the catalytic domain) and T389 and S404 (in the linker region), are rapamycin sensitive and flanked by bulky aromatic residues. Here we describe the identification and mutational analysis of three new phosphorylation sites, T367, S371, and T447, all of which have a recognition motif similar to that of the first set of sites. A mutation of T367 or T447 to either alanine or glutamic acid had no apparent effect on p70s6k activity, whereas similar mutations of S371 abolished kinase activity. Of these three sites and their surrounding motifs, only S371 is conserved in p70s6k homologs from Drosophila melanogaster, Arabidopsis thaliana, and Saccharomyces cerevisiae, as well as many members of the protein kinase C family. Serum stimulation increased S371 phosphorylation; unlike the situation for specific members of the protein kinase C family, where the homologous site is regulated by autophosphorylation, S371 phosphorylation is regulated by an external mechanism. Phosphopeptide analysis of S371 mutants further revealed that the loss of activity in these variants was paralleled by a block in serum-induced T389 phosphorylation, a phosphorylation site previously shown to be essential for kinase activity. Nevertheless, the substitution of an acidic residue at T389, which mimics phosphorylation at this site, did not rescue mutant p70s6k activity, indicating that S371 phosphorylation plays an independent role in regulating intrinsic kinase activity.

Amino Acid Sequence↗
PubMed1997

Florid psychopathology in patients receiving shocks from implanted cardioverter-defibrillators.

OBJECTIVES: To increase awareness of the potential for disabling anxiety and depression in patients receiving shocks from implanted cardioverter-defibrillators (ICDs). PATIENTS AND METHODS: ICDs are implanted in patients at this hospital for control of serious ventricular tachyarrhythmias inadequately controlled by drug treatment, who are unsuitable for map guided antiarrhythmic surgery. All are reviewed regularly at a dedicated ICD clinic and are advised to make contact between visits if they experience shocks. Symptoms of anxiety or depression were not actively sought, nor was a patient support group operating at the time of this data collection. When overt psychopathology was identified, patients were referred to a designated psychiatrist for management. RESULTS: Over a six year period, six (17%) of 35 patients with ICDs developed florid psychiatric problems after experiencing shocks. None had premorbid psychiatric predisposition. Of the six patients suffering severe psychiatric problems, four were men, their age range was 30-63 years, and left ventricular ejection fraction was 18-40%. All shocks were appropriate for clinical arrhythmias and ranged in frequency from two in six months to 111 in 24 hours. All six patients manifested severe anxiety, focused on fear of future shocks. Depression was also evident in three patients and two had become housebound. All responded within weeks to anxiolytic or antidepressant drugs, combined with relaxation and cognitive therapies. Ongoing psychiatric therapy was refused by one patient, and was required for between three and 18 months in the remainder. One patient died and one received a cardiac transplant during the follow up period (median 27.5 months, range 8-43). CONCLUSIONS: Because ICD implantation occurs against a complex medical background with inevitable psychological stress, all such patients should be considered at high risk for developing psychopathology.

Adult↗
PubMed1997

Sputum cytology: a limited role.

AIMS: To determine the cost and sensitivity of sputum cytology in routine use and to determine when sputum cytology is most appropriate. METHODS: A retrospective study, based on all sputum cytology requests received in five histopathology/cytopathology laboratories in Yorkshire from 1 January to 31 December 1993. Cytology findings were correlated with histological diagnosis or clinical outcome, and related to the speciality of the referring clinician. RESULTS: Laboratory practice and performance was similar in all five centres. The average laboratory cost of sputum cytology was 26.93. The mean absolute sensitivity was 36% and the specificity was 99.6%. The majority of specimens was submitted by general physicians or geriatricians. The largest proportion of positive specimens were submitted by chest physicians. CONCLUSIONS: Often sputum cytology is used inappropriately as a screening investigation on, or soon after, admission. In addition, it is used inappropriately before bronchoscopy. Sputum cytology should be limited to individuals in whom a histological diagnosis is desired, but in whom bronchoscopy is inappropriate or unsuccessful.

Bronchoscopy↗
PubMed1997

Differential stimulation of cytosolic phospholipase A2 by bradykinin in human cystic fibrosis cell lines.

Tracheal epithelial cells and skin fibroblasts from different cystic fibrosis (CF) patients bearing the deltaF508 mutation of cystic fibrosis transmembrane conductance regulator (CFTR) released more arachidonic acid in response to bradykinin than do other CF and normal cells. Immortalized tracheal epithelial cell lines were used as models to study the mechanisms of this dysregulation. An 85 kD cytosolic phospholipase A2 (cPLA2) was found in these cells and bradykinin increased its binding to membranes of deltaF508 cells (CFT-2) but not to those of a double heterozygous CF cells (CFT-1), or of control cells (NT-1). The expression of G alpha(q)/11 protein was also increased in deltaF508 cells, with increased stimulation of phosphatidylinositol diphosphate-specific phospholipase C (PLC) by bradykinin, and an early, transient activation of mitogen-activated protein (MAP) kinase. As the binding of cPLA2 to membranes is Ca2+-dependent, the increased coupling to PLC could cause the hypersensitivity to bradykinin. Comparison of the effects of bradykinin to those observed with thapsigargin, an inhibitor of calcium reuptake, suggests that the increase of intracellular calcium is not the only mechanism involved in arachidonic acid release by bradykinin in deltaF508 cells. The lack of effect of calcium ionophore A23187 or TPA on arachidonic acid release from any of the cell lines suggested that activation needs a PKC-independent cPLA2 phosphorylation step, perhaps via MAP kinase activation. The binding of cPLA2 to membranes after bradykinin stimulation still occurred in CFT2 cells (deltaF508) homogenized in EDTA, suggesting that a membrane component plus increased intracellular calcium influenced cPLA2 anchoring to membranes. The defective processing of deltaF508 CFTR seems to increase cPLA2 stimulation by bradykinin, since the bradykinin-stimulated release of arachidonic acid is reversed by growing cells at 28 degrees C for 48 h. The deltaF508 mutation of CFTR appears to increase the stimulation of cPLA2 by Gq-mediated receptors in a PKC-independent and MAP kinase-dependent manner. Hence normal CFTR, or normally processed deltaF508 CFTR, inhibit cPLA2 stimulation. The greater reactivity of deltaF508 CFTR cells to inflammatory mediators might be part of the increased sensitivity of CF patients to lung inflammation.

Bradykinin↗
PubMed1997

Relation of apolipoprotein E polymorphism to lipid metabolism in obese children.

To determine whether the risk of obesity-associated dyslipidemia in children is influenced by apolipoprotein E (apoE) polymorphism, we studied 137 obese, nongenetically related children aged 2.2-14.4 y (mean age, 9.9 +/- 3.1 y) with a weight-for-height excess of 43.7 +/- 17.9%. The apoE genotype was determined by studying specific DNA restriction patterns. Total cholesterol, HDL-cholesterol, and triglycerides were assayed in plasma before dietary treatment initiation. ApoE allele and phenotype distributions were comparable to those reported in the Caucasian population at large. Fifty-five children (41%) had elevated lipid levels. Compared with obese children with the epsilon3 or epsilon4 allele, those with the epsilon2 allele were more likely to have hypertriglyceridemia (19.5% versus 52.9%, p < 0.05) and had a higher mean triglyceride level: children with the epsilon4 allele were more likely to have a LDL-cholesterol elevation (34.7% versus 13.4%, p < 0.05). Our data demonstrate that, even in childhood, obesity is associated with a marked increase in the risk of lipoprotein abnormalities and that the latter are influenced by apoE polymorphism.

Adolescent↗
PubMed1997

Inflammatory bowel disease management. Some thoughts on future drug developments.

This article is intended to stimulate thought and focus on those areas where we feel advances in drug therapy for inflammatory bowel disease may occur. It is not an extensive review of current practice, although this is considered where it is thought to be pertinent to future developments. There are several excellent reviews of current practice which we do not attempt to repeat, nor do we give a comprehensive set of references, but cite well referenced reviews where necessary. New therapeutic developments should ideally stem from an understanding of the cause of pathogenesis of a condition; alternatively, established therapies may be modified or used as a basis for progress. Since the causes of both ulcerative colitis and Crohn's disease remain unknown, most forward thinking on drug development must come from current practice, but remain open to novel approaches. Our thoughts on possible future treatments for inflammatory bowel disease are somewhat selective, and because of their speculative nature are unlikely to coincide with those of others-only the future will reveal genuine advances as they become incorporated into established practice.

Adrenal Cortex Hormones↗
PubMed1997

Activation of phospholipase D by endothelin-1 in rat myometrium. Role of calcium and protein kinase C.

In rat myometrium labeled with [3H]myristic acid, endothelin (ET)-1 via ET(A) receptors stimulated, in the presence of 0.3% butanol, the formation of [3H]phosphatidylbutanol ([3H]PBut) as a result of phospholipase D activity. Fluoroaluminates increased [3H]PBut generation, which indicated that a heterotrimeric G protein was involved. The ET-1 effect was insensitive to pertussis toxin and was rapidly desensitized. The calcium ionophore ionomycin as well as 4beta-phorbol 12-myristate-13-acetate and 4beta-phorbol 12,13-dibutyrate also stimulated [3H]P-But production. Protein kinase C (PKC) inhibition, particularly with Ro-31-8220, and down-regulation of PKC by 4beta-phorbol 12-myristate-13-acetate, abrogated 4beta-phorbol 12,13-dibutyrate responses but partially reduced (50%) ET-1 and ionomycin stimulatory effects. [3H]PBut production induced by ionomycin depended on Ca++ influx, whereas that induced by 4beta-phorbol 12,13-dibutyrate did not. Decrease of extracellular Ca++ partially reduced (60%) ET-1 stimulation that was additionally attenuated (75%) by chelerythrine, a PKC inhibitor. The data indicate that in myometrium, phospholipase D was activated by PKC and Ca++, which both contribute at least partially to ET-1-mediated phospholipase D activation.

Animals↗
PubMed1997

BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group.

An account of familial aggregation in breast/ovarian cancer has become possible with the identification of BRCA1 germ-line mutations. We evaluated, for 249 individuals registered with the Institut Curie in Paris, the prior probability that an individual carried a mutation that predisposes to these diseases. We chose 160 women for BRCA1 analysis: 103 with a family history of breast cancer and 57 with a family history of breast-ovarian cancer. To detect small mutations, we generated and analyzed 35 overlapping genomic PCR products that cover the coding portion of the gene, by using denaturing gradient gel electrophoresis. Thirty-eight truncating mutations (32 frameshifts, 4 nonsense mutations, and 2 splice variants) were observed in 15% of women with a family history of breast cancer only and in 40% of those with a history of breast-ovarian cancer. Twelve of 25 distinct truncating mutations identified were novel and unique. Most BRCA1 mutations that had been reported more than five times in the Breast Cancer Information Core were present in our series. One mutation (5149del4) observed in two apparently unrelated families most likely originates from a common ancestor. The position of truncating mutations did not significantly affect the ratio of the risk of breast cancer to that of ovarian cancer. In addition, 15 DNA variants (14 missense mutations and 1 neutral mutation) were identified, 9 of which were novel. Indirect evidence suggests that seven of these mutations are deleterious.

Africa↗