Ali F

References (14)

Title : Benzimidazole-Based Schiff Base Hybrid Scaffolds: A Promising Approach to Develop Multi-Target Drugs for Alzheimer's Disease - Hussain_2023_Pharmaceuticals.(Basel)_16_
Author(s) : Hussain R , Khan S , Ullah H , Ali F , Khan Y , Sardar A , Iqbal R , Ataya FS , El-Sabbagh NM , Batiha GE
Ref : Pharmaceuticals (Basel) , 16 : , 2023
Abstract : A series of benzimidazole-based Schiff base derivatives (1-18) were synthesized and structurally elucidated through (1)H NMR, (13)C NMR and HREI-MS analysis. Subsequently, these synthetic derivatives were subjected to evaluation for their inhibitory capabilities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). All these derivatives showed significant inhibition against AChE with an IC(50) value in the range of 123.9 +/- 10.20 to 342.60 +/- 10.60 microM and BuChE in the range of 131.30 +/- 9.70 to 375.80 +/- 12.80 microM in comparison with standard Donepezil, which has IC(50) values of 243.76 +/- 5.70 microM (AChE) and 276.60 +/- 6.50 microM (BuChE), respectively. Compounds 3, 5 and 9 exhibited potent inhibition against both AChE and BuChE. Molecular docking studies were used to validate and establish the structure-activity relationship of the synthesized derivatives.
ESTHER : Hussain_2023_Pharmaceuticals.(Basel)_16_
PubMedSearch : Hussain_2023_Pharmaceuticals.(Basel)_16_
PubMedID: 37765088

Title : Lipidomic and transcriptional analysis of the linoleoyl-omega-hydroxyceramide biosynthetic pathway in human psoriatic lesions - Tyrrell_2021_J.Lipid.Res_62_100094
Author(s) : Tyrrell VJ , Ali F , Boeglin WE , Andrews R , Burston J , Birchall JC , Ingram JR , Murphy RC , Piguet V , Brash AR , O'Donnell VB , Thomas CP
Ref : J Lipid Res , 62 :100094 , 2021
Abstract : A complex assembly of lipids including fatty acids, cholesterol, and ceramides is vital to the integrity of the mammalian epidermal barrier. The formation of this barrier requires oxidation of the substrate fatty acid, linoleic acid (LA), which is initiated by the enzyme 12R-lipoxygenase (LOX). In the epidermis, unoxidized LA is primarily found in long-chain acylceramides termed esterified omega-hydroxy sphingosine (EOS)/phytosphingosine/hydroxysphingosine (collectively EOx). The precise structure and localization of LOX-oxidized EOx in the human epidermis is unknown, as is their regulation in diseases such as psoriasis, one of the most common inflammatory diseases affecting the skin. Here, using precursor LC/MS/MS, we characterized multiple intermediates of EOx, including 9-HODE, 9,10-epoxy-13-HOME, and 9,10,13-TriHOME, in healthy human epidermis likely to be formed via the epidermal LOX pathways. The top layers of the skin contained more LA, 9-HODE, and 9,10,13-TriHOME EOSs, whereas 9,10-epoxy-13-HOME EOS was more prevalent deeper in the stratum corneum. In psoriatic lesions, levels of native EOx and free HODEs and HOMEs were significantly elevated, whereas oxidized species were generally reduced. A transcriptional network analysis of human psoriatic lesions identified significantly elevated expression of the entire biosynthetic/metabolic pathway for oxygenated ceramides, suggesting a regulatory function for EOx lipids in reconstituting epidermal integrity. The role of these new lipids in progression or resolution of psoriasis is currently unknown. We also discovered the central coordinated role of the zinc finger protein transcription factor, ZIC1, in driving the phenotype of this disease. In summary, long-chain oxygenated ceramide metabolism is dysregulated at the lipidomic level in psoriasis, likely driven by the transcriptional differences also observed, and we identified ZIC1 as a potential regulatory target for future therapeutic interventions.
ESTHER : Tyrrell_2021_J.Lipid.Res_62_100094
PubMedSearch : Tyrrell_2021_J.Lipid.Res_62_100094
PubMedID: 34171322

Title : Organoselenium Compounds as Acetylcholinesterase Inhibitors: Evidence and Mechanism of Mixed Inhibition - Kumawat_2021_J.Phys.Chem.B__
Author(s) : Kumawat A , Raheem S , Ali F , Dar TA , Chakrabarty S , Rizvi MA
Ref : J Phys Chem B , : , 2021
Abstract : Acetylcholinesterase (AChE) inhibitors are actively used for the effective treatment of Alzheimer's disease. In recent years, the neuroprotective effects of organoselenium compounds such as ebselen and diselenides on the AChE activity have been investigated as potential therapeutic agents. In this work, we have carried out systematic kinetic and intrinsic fluorescence assays in combination with docking and molecular dynamics (MD) simulations to elucidate the molecular mechanism of the mixed inhibition of AChE by ebselen and diphenyl diselenide (DPDSe) molecules. Our MD simulations demonstrate significant heterogeneity in the binding modes and allosteric hotspots for DPDSe on AChE due to non-specific interactions. We have further identified that both ebselen and DPDSe can strongly bind around the peripheral anionic site (PAS), leading to non-competitive inhibition similar to other PAS-binding inhibitors. We also illustrate the entry of the DPDSe molecule into the gorge through a "side door", which offers an alternate entry point for AChE inhibitors as compared to the usual substrate entry point of the gorge. Together with results from experiments, these simulations provide mechanistic insights into the mixed type of inhibition for AChE using DPDSe as a promising inhibitor for AChE.
ESTHER : Kumawat_2021_J.Phys.Chem.B__
PubMedSearch : Kumawat_2021_J.Phys.Chem.B__
PubMedID: 33538163

Title : Protective Effect of Kaempferol on the Transgenic Drosophila Model of Alzheimer's Disease - Beg_2018_CNS.Neurol.Disord.Drug.Targets_17_421
Author(s) : Beg T , Jyoti S , Naz F , Rahul , Ali F , Ali SK , Reyad AM , Siddique YH
Ref : CNS Neurol Disord Drug Targets , 17 :421 , 2018
Abstract : BACKGROUND: Alzheimer's disease (AD) is characterized by the accumulation and deposition of beta-amyloid peptides leading to a progressive neuronal damage and cell loss. Besides several hypotheses for explaining the neurodegenerative mechanisms, oxidative stress has been considered to be one of them. Till date, there is no cure for AD, but the pathogenesis of the disease could be delayed by the use of natural antioxidants. In this context, we decided to study the effect of kaempferol against the transgenic Drosophila expressing human amyloid beta-42. METHOD: The AD flies were allowed to feed on the diet having 10, 20, 30 and 40microM of kaempferol for 30 days. After 30 days of exposure, the amyloid beta flies were studied for their climbing ability and Aversive Phototaxis Suppression assay. Amyloid beta flies head homogenate was prepared for estimating the oxidative stress markers, Caspase and acetylcholinesterase activity. RESULTS: The results of the present study reveal that the exposure of AD flies to kaempferol delayed the loss of climbing ability, memory, reduced the oxidative stress and acetylcholinesterase activity. CONCLUSION: Kaempferol could be used as a possible therapeutic agent against the progression of the Alzheimer's disease.
ESTHER : Beg_2018_CNS.Neurol.Disord.Drug.Targets_17_421
PubMedSearch : Beg_2018_CNS.Neurol.Disord.Drug.Targets_17_421
PubMedID: 29745345

Title : Therapeutic potential of luteolin in transgenic Drosophila model of Alzheimer's disease - Ali_2018_Neurosci.Lett_692_90
Author(s) : Ali F , Rahul , Jyoti S , Naz F , Ashafaq M , Shahid M , Siddique YH
Ref : Neuroscience Letters , 692 :90 , 2018
Abstract : A transgenic fly line expressing wild type human Abeta42 were exposed to luteolin mixed in diet at final concentration of 5, 10, 15 and 20muM. The climbing assay, activity pattern, life span, aversive phototaxis suppression assay (APS) along with the estimation of protein carbonyl content (PCC), glutathione-S-transferase (GSTs) activity, glutathione (GSH) content, lipid peroxidation (LPO), acetylcholinesterase activity (AChE), superoxide dismutase (SOD) activity, catalase (CAT) activity, caspase 3 and 9 activities in the brain of treated as well as untreated AD flies (Positive control) were studied. Histopathology of Drosophila brain sections was done by performing thioflavin-S, Bielschowsky's silver staining and toluidine blue staining. A dose-dependent increase in the life span, delay in the loss of climbing ability as well as activity was observed in AD flies exposed to luteolin compared to unexposed AD flies. A dose-dependent reduction in LPO, PCC, GST, AChE, SOD, CAT, caspase 9 and caspase 3 activity and an increase in the GSH content was also observed. Histopathological examination of fly brains using thioflavin-S and silver staining has revealed a significant dose-dependent reduction in the expression of Abeta42 peptides in AD fly groups exposed to 10, 15 and 20muM of luteolin. No gross morphological changes were observed in the brain sections of AD and control flies stained with toluidine blue. Molecular docking results have revealed that luteolin binds to AChE and Abeta42 at specific sites that might result in the inhibition of AChE and disaggregation/prevention of Abeta42 plaque formation.
ESTHER : Ali_2018_Neurosci.Lett_692_90
PubMedSearch : Ali_2018_Neurosci.Lett_692_90
PubMedID: 30420334

Title : Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases - Rahim_2016_Bioorg.Chem_68_30
Author(s) : Rahim F , Ullah H , Taha M , Wadood A , Javed MT , Rehman W , Nawaz M , Ashraf M , Ali M , Sajid M , Ali F , Khan MN , Khan KM
Ref : Bioorg Chem , 68 :30 , 2016
Abstract : To discover multifunctional agents for the treatment of Alzheimer's disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12+/-0.01, 8.12+/-0.01 and 8.41+/-0.06muM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50=0.85+/-0.0001muM). Three compounds 13, 24 and 3 having IC50 values 6.51+/-0.01, 9.22+/-0.07 and 37.82+/-0.14muM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50=0.04+/-0.0001muM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed.
ESTHER : Rahim_2016_Bioorg.Chem_68_30
PubMedSearch : Rahim_2016_Bioorg.Chem_68_30
PubMedID: 27441832

Title : Toxic potential of copper-doped ZnO nanoparticles in Drosophila melanogaster (Oregon R) - Siddique_2015_Toxicol.Mech.Methods_25_425
Author(s) : Siddique YH , Haidari M , Khan W , Fatima A , Jyoti S , Khanam S , Naz F , Rahul , Ali F , Singh BR , Beg T , Mohibullah , Naqvi AH
Ref : Toxicol Mech Methods , 25 :425 , 2015
Abstract : AIMS: In the present study, copper-doped ZnO nanoparticles (doped ZnO NPs Cu) were synthesized, characterized and evaluated for their possible toxic effects in Drosophila melanogaster (Oregon R). METHODS AND
RESULTS: X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and energy dispersive X-ray spectrometry confirm the formation of doped ZnO NPs Cu. Doped ZnO NPs Cu (3%) were mixed in the diet at final concentrations of 1, 2, 4 and 8 microg/microl. The starved male flies were allowed to feed on it for 4 days. After completion of the desired duration, climbing ability, activity pattern, activity of acetylcholinesterase (AChE), glutathione (GSH), glutathione-S-transferase (GST), lipid peroxidation (LPO), total protein content and caspases were studied. SDS-PAGE was also performed for whole fly homogenate of control as well as treated flies. No loss in the climbing and activity pattern was observed at the selected doses of doped ZnO NPs Cu. No significant change in the levels of AChE, GSH, GST, LPO, caspase 9/3 and total protein content was observed. The brain sections showed no gross changes in the structure and SDS-PAGE patterns also revealed no change in the protein expression.
CONCLUSIONS: The results suggest that doped ZnO NPs Cu are non-toxic at 1, 2, 4 and 8 microg/microl of concentration in D. melanogaster.
ESTHER : Siddique_2015_Toxicol.Mech.Methods_25_425
PubMedSearch : Siddique_2015_Toxicol.Mech.Methods_25_425
PubMedID: 26000624

Title : Antioxidant, cholinesterase inhibition activities and essential oil analysis of Nelumbo nucifera seeds - Khan_2015_Nat.Prod.Res__1
Author(s) : Khan S , Khan H , Ali F , Ali N , Khan FU , Khan SU
Ref : Nat Prod Res , :1 , 2015
Abstract : Nelumbo nucifera seeds' essential oil (EO), crude extract and subsequent fractions were evaluated for their DPPH, ABTS and superoxide anion-free radical scavenging and cholinesterase inhibitory activities. The ethyl acetate fraction and EO showed outstanding antioxidant activities with IC50 values of 191, 450 mug/mL (DPPH), 123, 221 mug/mL (ABTS) and 69, 370 mug/mL (superoxide anion). The ethyl acetate fraction and EO also caused significant inhibition of acetylcholinesterase and butyrylcholinesterase with IC50 values of 70 +/- 0.6, 64 +/- 0.8 and 75 +/- 0.3, 58 +/- 0.2, in dose-dependent manner. The first ever gas chromatography-mass spectrometry analysis of the EO obtained from N. nucifera seeds resulted in identification of 19 constituents, mainly comprised of oxygenated sesquiterpenes responsible for their promising bioactivity. The crude and fractions revealed the presence of saponins, flavonoids, steroids, alkaloids, terpenoids and cardiac glycosides in phytochemical investigation.
ESTHER : Khan_2015_Nat.Prod.Res__1
PubMedSearch : Khan_2015_Nat.Prod.Res__1
PubMedID: 26212099

Title : Evaluation of the toxic potential of calcium carbide in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg - Danish_2015_Chemosphere_139_469
Author(s) : Danish M , Fatima A , Khanam S , Jyoti S , Rahul , Ali F , Naz F , Siddique YH
Ref : Chemosphere , 139 :469 , 2015
Abstract : In the present study the toxic potential of calcium carbide (CaC2) was studied on the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9. The third instar larvae were exposed to 2, 4, 8, 16 and 32x10-3g/ml of CaC2 in diet for 24h. The results reveal that the dose 2x10-3g/ml was not toxic but the remaining doses showed a dose dependent significant increase in the hsp70 expression, beta-galactosidase activity, tissue damage, oxidative stress markers (lipid peroxidation and protein carbonyl content), glutathione-S-transferase activity, expression of Caspase 3 and 9, apoptotic index and DNA damage (midgut cells). A significant reduction as compared to control group in total protein, glutathione content and acetylcholinesterase activity was also observed. The Inductively Coupled Plasma Atomic Emission Spectroscopy analysis (ICPAES) reveals the presence of copper, iron, sodium, aluminium, manganese, calcium, nickel and mercury. The toxic effects of CaC2 in the present study may be attributed to the impurities present in it.
ESTHER : Danish_2015_Chemosphere_139_469
PubMedSearch : Danish_2015_Chemosphere_139_469
PubMedID: 26298668

Title : New Cholinesterase Inhibitory Constituents from Lonicera quinquelocularis - Khan_2014_PLoS.One_9_e94952
Author(s) : Khan D , Khan HU , Khan F , Khan S , Badshah S , Khan AS , Samad A , Ali F , Khan I , Muhammad N
Ref : PLoS ONE , 9 :e94952 , 2014
Abstract : A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera quinquelocularis (whole plant) led to the first time isolation of one new phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate (3) and two new benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4) and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5) along with two known compounds bis (2-ethylhexyl phthalate (1) and dioctyl phthalate (2). Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (1-5) were tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in dose dependent manner. The IC50 (50% inhibitory effect) values of compounds 3 and 5 against AChE were 1.65 and 3.43 microM while the values obtained against BChE were 5.98 and 9.84 microM respectively. Compounds 2 and 4 showed weak inhibition profile.
ESTHER : Khan_2014_PLoS.One_9_e94952
PubMedSearch : Khan_2014_PLoS.One_9_e94952
PubMedID: 24733024

Title : Two new cholinesterase inhibitors asiatoates A and B from Buddleja asiatica - Ali_2013_J.Asian.Nat.Prod.Res_15_631
Author(s) : Ali F , Khan HU , Afzal M , Samad A , Khan SU , Ali I
Ref : J Asian Nat Prod Res , 15 :631 , 2013
Abstract : Two new benzoates, asiatoate A (1) and asiatoate B (2), have been isolated from the ethyl acetate soluble fraction of Buddleja asiatica whole plant. Their structures were elucidated with the help of spectroscopic data. Both showed significant inhibitory effect on acetylcholinesterase (AChE) and butylcholinesterase (BChE) in a dose-dependent manner. The IC50 values of compounds 1-2 were 5.54 and 8.34 muM against AChE while 30.94 and 35.94 muM against BChE, respectively.
ESTHER : Ali_2013_J.Asian.Nat.Prod.Res_15_631
PubMedSearch : Ali_2013_J.Asian.Nat.Prod.Res_15_631
PubMedID: 23659547

Title : Structural insights to investigate Conypododiol as a dual cholinesterase inhibitor from Asparagus adscendens - Khan_2010_Fitoterapia_81_1020
Author(s) : Khan I , Nisar M , Khan N , Saeed M , Nadeem S , Fazal ur R , Ali F , Karim N , Kaleem WA , Qayum M , Ahmad H , Khan IA
Ref : Fitoterapia , 81 :1020 , 2010
Abstract : The main aim of the current study was to explore molecular insights for potentially new dual cholinesterase inhibitor(s) from Asparagus adscendens via molecular docking. This medicinal plant is traditionally used as a nerve tonic and remedy for memory impairments. Conypododiol was isolated from the chloroform fraction of methanolic extract of A. adscendens, based on bioactivity guided isolation. Conypododiol exhibited significant inhibition of both acetylcholinesterase and butyrylcholinesterase, having the IC(50) values 2.17 +/- 0.1 muM and 11.21 +/- 0.1 muM, respectively. IC(50) values of the standard compound Galanthamine for both the enzymes were 0.537 +/- 0.018 muM and 8.6 +/- 0.27 muM, respectively. Based on MTT cytotoxicity assay, Conypododiol was found safe against LCMK-2 monkey kidney epithelial cells and mice hepatocytes. Molecular docking studies revealed the hydrogen bonding interactions of Conypododiol with His440 and Ser200 at esteratic site (ES), and also with Tyr334 at peripheral anionic site (PAS) of the aromatic gorge of acetylcholinesterase. Simultaneous contacts of Conypododiol with PAS and ES shows its significance as a bivalent ligand. This preliminary study highlighted the potential of Conypododiol to be further developed and modified as new lead compound identified by its folk use.
ESTHER : Khan_2010_Fitoterapia_81_1020
PubMedSearch : Khan_2010_Fitoterapia_81_1020
PubMedID: 20600681

Title : A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome - Mural_2002_Science_296_1661
Author(s) : Mural RJ , Adams MD , Myers EW , Smith HO , Miklos GL , Wides R , Halpern A , Li PW , Sutton GG , Nadeau J , Salzberg SL , Holt RA , Kodira CD , Lu F , Chen L , Deng Z , Evangelista CC , Gan W , Heiman TJ , Li J , Li Z , Merkulov GV , Milshina NV , Naik AK , Qi R , Shue BC , Wang A , Wang J , Wang X , Yan X , Ye J , Yooseph S , Zhao Q , Zheng L , Zhu SC , Biddick K , Bolanos R , Delcher AL , Dew IM , Fasulo D , Flanigan MJ , Huson DH , Kravitz SA , Miller JR , Mobarry CM , Reinert K , Remington KA , Zhang Q , Zheng XH , Nusskern DR , Lai Z , Lei Y , Zhong W , Yao A , Guan P , Ji RR , Gu Z , Wang ZY , Zhong F , Xiao C , Chiang CC , Yandell M , Wortman JR , Amanatides PG , Hladun SL , Pratts EC , Johnson JE , Dodson KL , Woodford KJ , Evans CA , Gropman B , Rusch DB , Venter E , Wang M , Smith TJ , Houck JT , Tompkins DE , Haynes C , Jacob D , Chin SH , Allen DR , Dahlke CE , Sanders R , Li K , Liu X , Levitsky AA , Majoros WH , Chen Q , Xia AC , Lopez JR , Donnelly MT , Newman MH , Glodek A , Kraft CL , Nodell M , Ali F , An HJ , Baldwin-Pitts D , Beeson KY , Cai S , Carnes M , Carver A , Caulk PM , Center A , Chen YH , Cheng ML , Coyne MD , Crowder M , Danaher S , Davenport LB , Desilets R , Dietz SM , Doup L , Dullaghan P , Ferriera S , Fosler CR , Gire HC , Gluecksmann A , Gocayne JD , Gray J , Hart B , Haynes J , Hoover J , Howland T , Ibegwam C , Jalali M , Johns D , Kline L , Ma DS , MacCawley S , Magoon A , Mann F , May D , McIntosh TC , Mehta S , Moy L , Moy MC , Murphy BJ , Murphy SD , Nelson KA , Nuri Z , Parker KA , Prudhomme AC , Puri VN , Qureshi H , Raley JC , Reardon MS , Regier MA , Rogers YH , Romblad DL , Schutz J , Scott JL , Scott R , Sitter CD , Smallwood M , Sprague AC , Stewart E , Strong RV , Suh E , Sylvester K , Thomas R , Tint NN , Tsonis C , Wang G , Williams MS , Williams SM , Windsor SM , Wolfe K , Wu MM , Zaveri J , Chaturvedi K , Gabrielian AE , Ke Z , Sun J , Subramanian G , Venter JC , Pfannkoch CM , Barnstead M , Stephenson LD
Ref : Science , 296 :1661 , 2002
Abstract : The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.
ESTHER : Mural_2002_Science_296_1661
PubMedSearch : Mural_2002_Science_296_1661
PubMedID: 12040188
Gene_locus related to this paper: mouse-ABH15 , mouse-Ces3b , mouse-Ces4a , mouse-dpp4 , mouse-FAP , mouse-Lipg , mouse-Q8C1A9 , mouse-rbbp9 , mouse-SERHL , mouse-SPG21 , mouse-w4vsp6

Title : The sequence of the human genome - Venter_2001_Science_291_1304
Author(s) : Venter JC , Adams MD , Myers EW , Li PW , Mural RJ , Sutton GG , Smith HO , Yandell M , Evans CA , Holt RA , Gocayne JD , Amanatides P , Ballew RM , Huson DH , Wortman JR , Zhang Q , Kodira CD , Zheng XH , Chen L , Skupski M , Subramanian G , Thomas PD , Zhang J , Gabor Miklos GL , Nelson C , Broder S , Clark AG , Nadeau J , McKusick VA , Zinder N , Levine AJ , Roberts RJ , Simon M , Slayman C , Hunkapiller M , Bolanos R , Delcher A , Dew I , Fasulo D , Flanigan M , Florea L , Halpern A , Hannenhalli S , Kravitz S , Levy S , Mobarry C , Reinert K , Remington K , Abu-Threideh J , Beasley E , Biddick K , Bonazzi V , Brandon R , Cargill M , Chandramouliswaran I , Charlab R , Chaturvedi K , Deng Z , Di Francesco V , Dunn P , Eilbeck K , Evangelista C , Gabrielian AE , Gan W , Ge W , Gong F , Gu Z , Guan P , Heiman TJ , Higgins ME , Ji RR , Ke Z , Ketchum KA , Lai Z , Lei Y , Li Z , Li J , Liang Y , Lin X , Lu F , Merkulov GV , Milshina N , Moore HM , Naik AK , Narayan VA , Neelam B , Nusskern D , Rusch DB , Salzberg S , Shao W , Shue B , Sun J , Wang Z , Wang A , Wang X , Wang J , Wei M , Wides R , Xiao C , Yan C , Yao A , Ye J , Zhan M , Zhang W , Zhang H , Zhao Q , Zheng L , Zhong F , Zhong W , Zhu S , Zhao S , Gilbert D , Baumhueter S , Spier G , Carter C , Cravchik A , Woodage T , Ali F , An H , Awe A , Baldwin D , Baden H , Barnstead M , Barrow I , Beeson K , Busam D , Carver A , Center A , Cheng ML , Curry L , Danaher S , Davenport L , Desilets R , Dietz S , Dodson K , Doup L , Ferriera S , Garg N , Gluecksmann A , Hart B , Haynes J , Haynes C , Heiner C , Hladun S , Hostin D , Houck J , Howland T , Ibegwam C , Johnson J , Kalush F , Kline L , Koduru S , Love A , Mann F , May D , McCawley S , McIntosh T , McMullen I , Moy M , Moy L , Murphy B , Nelson K , Pfannkoch C , Pratts E , Puri V , Qureshi H , Reardon M , Rodriguez R , Rogers YH , Romblad D , Ruhfel B , Scott R , Sitter C , Smallwood M , Stewart E , Strong R , Suh E , Thomas R , Tint NN , Tse S , Vech C , Wang G , Wetter J , Williams S , Williams M , Windsor S , Winn-Deen E , Wolfe K , Zaveri J , Zaveri K , Abril JF , Guigo R , Campbell MJ , Sjolander KV , Karlak B , Kejariwal A , Mi H , Lazareva B , Hatton T , Narechania A , Diemer K , Muruganujan A , Guo N , Sato S , Bafna V , Istrail S , Lippert R , Schwartz R , Walenz B , Yooseph S , Allen D , Basu A , Baxendale J , Blick L , Caminha M , Carnes-Stine J , Caulk P , Chiang YH , Coyne M , Dahlke C , Mays A , Dombroski M , Donnelly M , Ely D , Esparham S , Fosler C , Gire H , Glanowski S , Glasser K , Glodek A , Gorokhov M , Graham K , Gropman B , Harris M , Heil J , Henderson S , Hoover J , Jennings D , Jordan C , Jordan J , Kasha J , Kagan L , Kraft C , Levitsky A , Lewis M , Liu X , Lopez J , Ma D , Majoros W , McDaniel J , Murphy S , Newman M , Nguyen T , Nguyen N , Nodell M , Pan S , Peck J , Peterson M , Rowe W , Sanders R , Scott J , Simpson M , Smith T , Sprague A , Stockwell T , Turner R , Venter E , Wang M , Wen M , Wu D , Wu M , Xia A , Zandieh A , Zhu X
Ref : Science , 291 :1304 , 2001
Abstract : A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.
ESTHER : Venter_2001_Science_291_1304
PubMedSearch : Venter_2001_Science_291_1304
PubMedID: 11181995
Gene_locus related to this paper: human-AADAC , human-ABHD1 , human-ABHD10 , human-ABHD11 , human-ACHE , human-BCHE , human-LDAH , human-ABHD18 , human-CMBL , human-ABHD17A , human-KANSL3 , human-LIPA , human-LYPLAL1 , human-NDRG2 , human-NLGN3 , human-NLGN4X , human-NLGN4Y , human-PAFAH2 , human-PREPL , human-RBBP9 , human-SPG21