Biomedical subjects

X Chen

Publications and source records attributed to X Chen.

At least 289 records · Page 16Linked to original sources

PubMed2001

Isoquinoline alkaloids from Thalictrum delavayi.

Two new protoberberine alkaloids, 2,3,9,10-dimethylenedioxy-8-oxoprotoberberine (1) and 2,3,9,10-dimethylenedioxy-1,8-dihydroxyprotoberberine (2), together with nine known isoquinoline-type alkaloids were isolated from the roots of Thalictrum delavayi. Their structures were elucidated by spectral methods. Among these compounds, pseudoprotopine showed competitive inhibition activity by DA receptor binding assay (D1) in vitro. The competitive inhibitions were 87.5% (10(-4) M) and 15.6% (10(-6) M), respectively.

Alkaloids↗

PubMed2001

Isoflavones inhibit proliferation of ovarian cancer cells in vitro via an estrogen receptor-dependent pathway.

Incidence rates of ovarian cancer remain lowest in Asian nations, which consume diets rich in soy products, whereas they remain among the highest in the United States and other Western nations, which consume low amounts of soy foods. The hypothesis of this study is that soy-derived isoflavones inhibit the proliferation of ovarian cancer cells in vitro by regulating cytokine synthesis. Cell proliferation was evaluated by bromodeoxyuridine and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA synthesis of Caov-3 and NIH:OVCAR-3, two ovarian cancer cell lines, was significantly inhibited by genistein or daidzein at dietarily relevant concentrations (10(-8)-10(-10) M). Also, the number of viable cells was significantly lower (45-75%) in all isoflavone-treated groups than in the control group (P < 0.01). The addition of ICI-182780, an estrogen antagonist, blocked these inhibitory effects. In addition, interleukin-6 synthesis by these two cell lines was inhibited by genistein or daidzein; production was decreased by approximately 20% compared with the control group (P < 0.05). In contrast, transforming growth factor-beta 1 production in ovarian cancer cells incubated with genistein or daidzein was significantly greater, i.e., by approximately 30%, than in the control group (P < 0.05). Addition of ICI-182780 also neutralized the effects of isoflavones on the production of these two cytokines by ovarian cancer cells. In summary, genistein and daidzein independently modify cytokine production and reduce ovarian cancer cell proliferation via, at least in part, an estrogen receptor-dependent pathway.

Cell Division↗

PubMed2001

Metal response element (MRE)-binding transcription factor-1 (MTF-1): structure, function, and regulation.

Metal-responsive control of the expression of genes involved in metal metabolism and metal homeostasis allows an organism to tightly regulate the free or bioavailable concentration of beneficial metal ions, such as zinc, copper, and iron, within an acceptable range, while efficiently removing nonbeneficial or toxic metals. Emerging evidence also suggests that metal homeostasis is intimately coupled to the oxidative stress response in many cell types. The expression of genes that encode metallothioneins in all vertebrate cells is strongly induced by potentially toxic concentrations of zinc and cadmium, as well as in response to strong oxidizing agents, including hydrogen peroxide. This induction requires a cis-acting DNA element, termed a metal response element (MRE), and MRE-binding transcription factor-1 (MTF-1), a Cys2-His2 zinc finger protein. This review summarizes recent progress that has been made toward understanding the structure, function, and metalloregulation of mammalian MTF-1.

Allosteric Regulation↗

PubMed2001

An information-based sequence distance and its application to whole mitochondrial genome phylogeny.

MOTIVATION: Traditional sequence distances require an alignment and therefore are not directly applicable to the problem of whole genome phylogeny where events such as rearrangements make full length alignments impossible. We present a sequence distance that works on unaligned sequences using the information theoretical concept of Kolmogorov complexity and a program to estimate this distance. RESULTS: We establish the mathematical foundations of our distance and illustrate its use by constructing a phylogeny of the Eutherian orders using complete unaligned mitochondrial genomes. This phylogeny is consistent with the commonly accepted one for the Eutherians. A second, larger mammalian dataset is also analyzed, yielding a phylogeny generally consistent with the commonly accepted one for the mammals. AVAILABILITY: The program to estimate our sequence distance, is available at http://www.cs.cityu.edu.hk/~cssamk/gencomp/GenCompress1.htm. The distance matrices used to generate our phylogenies are available at http://www.math.uwaterloo.ca/~mli/distance.html.

Animals↗

PubMed2001

Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype.

The phase II glutathione S-transferases (GSTs) GSTT1, GSTM1 and GSTP1 catalyse glutathione-mediated reduction of exogenous and endogenous electrophiles. These GSTs have broad and overlapping substrate specificities and it has been hypothesized that allelic variants associated with less effective detoxification of potential carcinogens may confer an increased susceptibility to cancer. To assess the role of GST gene variants in ovarian cancer development, we screened 285 epithelial ovarian cancer cases and 299 unaffected controls for the GSTT1 deletion (null) variant, the GSTM1 deletion (null) variant and the GSTP1 codon 104 A-->G Ile-->Val amino acid substitution variant. The frequencies of the GSTT1, GSTM1 and GSTP1 polymorphic variants did not vary with tumour behaviour (low malignant potential or invasive) or p53 immunohistochemical status. There was a suggestion that ovarian cancers of the endometrioid or clear cell histological subtype had a higher frequency of the GSTT1 and GSTM1 deletion genotype than other histological subgroups. The GSTT1, GSTM1 and GSTP1 genotype distributions did not differ significantly between unaffected controls and ovarian cancer cases (overall or invasive cancers only). However, the GSTM1 null genotype was associated with increased risk of endometrioid/clear cell invasive cancer [age-adjusted OR (95% CI) = 2.04 (1.01-4.09), P = 0.05], suggesting that deletion of GSTM1 may increase the risk of ovarian cancer of these histological subtypes specifically. This marginally significant finding will require verification by independent studies.

Adenocarcinoma, Clear Cell↗

PubMed2001

No significant association between progesterone receptor exon 4 Val660Leu G/T polymorphism and risk of ovarian cancer.

Epidemiological studies suggest that ovarian cancer is an endocrine-related tumour, and progesterone exposure specifically may decrease the risk of ovarian cancer. To assess whether the progesterone receptor (PR) exon 4 valine to leucine amino acid variant is associated with specific tumour characteristics or with overall risk of ovarian cancer, we examined 551 cases of epithelial ovarian cancer and 298 unaffected controls for the underlying G-->T nucleotide substitution polymorphism. Stratification of the ovarian cancer cases according to tumour behaviour (low malignant potential or invasive), histology, grade or stage failed to reveal any heterogeneity with respect to the genotype defined by the PR exon 4 polymorphism. Furthermore, the genotype distribution did not differ significantly between ovarian cancer cases and unaffected controls. Compared with the GG genotype, the age-adjusted odds ratio (95% confidence interval) for risk of ovarian cancer was 0.78 (0.57-1.08) for the GT genotype, and 1.39 (0.47-4.14) for the TT genotype. In conclusion, the PR exon 4 codon 660 leucine variant encoded by the T allele does not appear to be associated with ovarian tumour behaviour, histology, stage or grade. This variant is also not associated with an increased risk of ovarian cancer, and is unlikely to be associated with a large decrease in ovarian cancer risk, although we cannot rule out a moderate inverse association between the GT genotype and ovarian cancer.

Base Sequence↗

PubMed2001

Esophageal adenocarcinoma: a review and perspectives on the mechanism of carcinogenesis and chemoprevention.

The incidence rate of esophageal adenocarcinoma (EAC) has increased sharply in the past 30 years. Many risk factors have been identified and gastroesophageal reflux disease (GERD) is the most important one. Columnar-lined esophagus, resulting from GERD, is recognized as a key precursor lesion of EAC. In this article, we review the studies on EAC in humans and animal models. We propose that the pathogenesis of EAC is mainly driven by inflammation and oxidative stress, which are augmented by iron overload. The overproduction of prostaglandin E2 and leukotriene B4 and overexpression of their receptors are believed to be major factors in exacerbating inflammation and oxidative stress. Based on this mechanistic understanding, antioxidants, inhibitors of arachidonic acid metabolism enzymes and receptor antagonists of certain eicosanoids are proposed as potential chemopreventive agents for EAC in future studies.

Adenocarcinoma↗

PubMed2001

Regulation of intracellular trafficking of the EGF receptor by Rab5 in the absence of phosphatidylinositol 3-kinase activity.

Rab5 and phosphatidylinositol 3-kinase (PI3K) have been proposed to co-regulate receptor endocytosis by controlling early endosome fusion. However, in this report we demonstrate that inhibition of epidermal growth factor (EGF)-stimulated PI3K activity by expression of the kinase-deficient PI3K p110 subunit (p110delta kin) does not block the lysosomal targeting and degradation of the EGF receptor (EGFR). Moreover, inhibition of total PI3K activity by wortmannin or LY294002 significantly enlarges EGFR-containing endosomes and dissociates the early-endosomal autoantigen EEA1 from membrane fractions. However, this does not block the lysosomal targeting and degradation of EGFR. In contrast, transfection of cells with mutant Rab5 S34N or microinjection of anti-Rabaptin5 antibodies inhibits EGFR endocytosis. Our results, therefore, demonstrate that PI3K is not universally required for the regulation of receptor intracellular trafficking. The present work suggests that the intracellular trafficking of EGFR is controlled by a novel endosome fusion pathway that is regulated by Rab5 in the absence of PI3K, rather than by the previously defined endosome fusion pathway that is co-regulated by Rab5 and PI3K.

Androstadienes↗

PubMed2001

Regulation of epidermal growth factor receptor endocytosis by wortmannin through activation of Rab5 rather than inhibition of phosphatidylinositol 3-kinase.

The involvement of phosphatidylinositol 3-kinase (PI3K) in membrane trafficking in mammalian cells has largely come from experiments with wortmannin. This compound inhibits endosome fusion in vitro, possibly by inhibiting the production of phosphatidylinositol (PtdIns)-3-P, which co-regulates EEA1 with Rab5. However, the results from wortmannin inhibition experiments performed in vivo differ significantly. We have recently shown that wortmannin enlarges endosomes containing the epidermal growth factor receptor (EGFR) and enhances the lysosomal degradation of EGFR. In this report, we demonstrate that addition of the PI3K reaction products does not suppress wortmannin-induced enlargement of EGFR-containing endosomes and enhancement of EGFR degradation. Moreover, the effects of wortmannin on the intracellular trafficking of EGFR mimic those of the permanently activated Rab5 mutant, Rab5 Q79L, which stimulates endosome fusion. We also found that an inactive Rab5 mutant, Rab5 S34N, blocks wortmannin-induced endosome enlargement and that wortmannin stimulates the activation of Rab5. We further showed that wortmannin reduced the membrane association of p120 Ras GTPase-activating protein (GAP) and inhibited the interaction between Rab5 and p120 Ras GAP. We conclude that wortmannin alters intracellular trafficking of EGFR by activating Rab5 rather than by inhibiting PI3K.

Androstadienes↗

PubMed2001

An extract of Lagerstroemia speciosa L. has insulin-like glucose uptake-stimulatory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells.

The effects of extracts isolated from Lagerstroemia speciosa L. (banaba) on glucose transport and adipocyte differentiation in 3T3-L1 cells were studied. Glucose uptake-inducing activity of banaba extract (BE) was investigated in differentiated adipocytes using a radioactive assay, and the ability of BE to induce differentiation in preadipocytes was examined by Northern and Western blot analyses. The hot water BE and the banaba methanol eluent (BME) stimulated glucose uptake in 3T3-L1 adipocytes with an induction time and a dose-dependent response similar to those of insulin. Furthermore, there were no additive or synergistic effects found between BE and insulin on glucose uptake, and the glucose uptake activity of insulin could be reduced to basal levels by adding increasing amounts of BE. Unlike insulin, BE did not induce adipocyte differentiation in the presence of 3-isobutyl-1-methylxanthine (IBMX) and dexamethasone (DEX). BE inhibited the adipocyte differentiation induced by insulin plus IBMX and DEX (IS-IBMX-DEX) of 3T3-L1 preadipocytes in a dose-dependent manner. The differences in the glucose uptake and differentiation inhibitory activities between untreated cells and those treated with BE were significant (P < 0.01). The inhibitory activity was further demonstrated by drastic reductions of peroxisome proliferator-activated receptor gamma2 (PPARgamma2) mRNA and glucose transporter-4 (GLUT4) protein in cells induced from preadipocytes with IS-IBMX-DEX in the presence of BE. The unique combination of a glucose uptake stimulatory activity, the absence of adipocyte differentiation activity and effective inhibition of adipocyte differentiation induced by IS-IBMX-DEX in 3T3-L1 cells suggest that BE may be useful for prevention and treatment of hyperglycemia and obesity in type II diabetics.

1-Methyl-3-isobutylxanthine↗

PubMed2001

An aspartic proteinase expressed in the yolk sac and neonatal stomach of the mouse.

A murine aspartic proteinase, described herein, is intermediate in amino acid sequence identity between the placentally produced pregnancy-associated glycoproteins (PAGs) and gastric pepsins. While PAGs are secreted products of placental trophoblast tissue of ungulates and most are not believed to function proteolytically, pepsins are digestive enzymes. The cDNA for this aspartic proteinase was amplified by reverse transcription-polymerase chain reaction from RNA extracted from murine placentas and neonatal stomachs. The open reading frame encoded a 387-amino acid polypeptide with a 15-residue signal sequence. The enzyme most resembled pepsinogen F (a protein identified in the stomachs of neonatal rabbits and rats) and PAG-like proteins cloned from equine and feline placentae. In the stomach, both its mRNA and protein were expressed in gastric chief cells of preweaned neonates. Within the placenta, its mRNA was present in both the parietal and visceral yolk sacs. However, the protein was most prevalent in the visceral yolk sac, with little detectable in the parietal yolk sac. The recombinant protein was expressed in Escherichia coli. This protein was capable of self-activation and exhibited proteolytic activity toward casein. The presence of this enzyme in two organs involved in the selective transcellular transport of proteins suggests that it has specialized digestive functions.

Amino Acid Sequence↗

PubMed2001

The effect of timing of dolasetron administration on its efficacy as a prophylactic antiemetic in the ambulatory setting.

UNLABELLED: Dolasetron (12.5 mg IV) is effective in both preventing and treating postoperative nausea and vomiting (PONV) after ambulatory surgery. However, the optimal timing of dolasetron administration and its effect on the patient's quality of life after discharge have not been established. One-hundred-five healthy, consenting women undergoing gynecologic laparoscopic procedures with a standardized general anesthetic technique were enrolled in this randomized, double-blinded study. Group 1 received dolasetron 12.5 mg IV 10-15 min before the induction of anesthesia; Group 2 received dolasetron 12.5 mg IV at the end of the laparoscopy (79 +/- 48 min later than Group 1); and Group 3 received dolasetron 12.5 mg IV at the end of anesthesia (93 +/- 52 min later than Group 1). The incidence of PONV, complete responses (defined as no emetic episodes and no rescue medication within the 24-h period after anesthesia), recovery profiles, and patient satisfaction were recorded. In the postanesthesia care unit and during the 24-h follow-up period, the incidence of nausea and vomiting, as well as the need for rescue antiemetics, did not differ significantly among the three groups. The percentages of patients with complete responses to the study drug within the first postoperative 24 h were also similar in all three groups (55%, 59%, and 52% for Groups 1, 2, and 3, respectively). The early and intermediate recovery profiles, including resumption of a normal diet and patient satisfaction with the control of PONV, were not different among the three study groups. Dolasetron 12.5 mg IV administered before the induction of anesthesia is as effective as dolasetron given at the end of laparoscopy or at the end of anesthesia in preventing PONV after outpatient laparoscopy. IMPLICATIONS: The timing of dolasetron administration appears to have little effect on its efficacy when administered as a prophylactic antiemetic in the ambulatory setting.

Adult↗

PubMed2001

The recovery of cognitive function after general anesthesia in elderly patients: a comparison of desflurane and sevoflurane.

UNLABELLED: We evaluated the cognitive recovery profiles in elderly patients after general anesthesia with desflurane or sevoflurane. After IRB approval, 70 ASA physical status I-III consenting elderly patients (> or =65 yr old) undergoing total knee or hip replacement procedures were randomly assigned to one of two general anesthetic groups. Propofol and fentanyl were administered for induction of anesthesia, followed by either desflurane 2%-4% or sevoflurane 1%-1.5% with nitrous oxide 65% in oxygen. The desflurane (2.5 +/- 0.6 MAC. h) and sevoflurane (2.7 +/- 0.5 MAC. h) concentrations were adjusted to maintain comparable depths of hypnosis using the electroencephalogram bispectral index monitor. The Mini-Mental State (MMS) test was used to assess cognitive function preoperatively and postoperatively at 1, 3, 6, and 24-h intervals. The use of desflurane was associated with a more rapid emergence from anesthesia (6.3 +/- 2.4 min versus 8.0 +/- 2.8 min) and a shorter length of stay in the postanesthesia care unit (213 +/- 66 min versus 241 +/- 87 min). However, there were no significant differences between the Desflurane and the Sevoflurane groups when the MMS scores were compared preoperatively, and postoperatively at 1, 3, 6, and 24 h. Compared with the preoperative (baseline) MMS scores, the values were significantly decreased at 1 h postoperatively (27.8 +/- 1.7 versus 29.5 +/- 0.5 in the Desflurane group, and 27.4 +/- 1.7 versus 29.2 +/- 1.0 in the Sevoflurane group, respectively). However, the MMS scores returned to preoperative baseline levels within 6 h after surgery. At 1 h and 3 h after surgery, 51% and 11% (versus 57% and 9%) of patients in the Desflurane (versus Sevoflurane) Group experienced cognitive impairment. In conclusion, desflurane is associated with a faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of cognitive function was similar after desflurane and sevoflurane-based anesthesia. IMPLICATIONS: Desflurane was associated with a faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of cognitive function was similar with both volatile anesthetics.

Aged↗

PubMed2001

Different inhibitory effects of volatile anesthetics on T- and L-type voltage-dependent Ca2+ channels in porcine tracheal and bronchial smooth muscles.

BACKGROUND: The distal airway is more important in the regulation of airflow resistance than is the proximal airway, and volatile anesthetics have a greater inhibitory effect on distal airway muscle tone. The authors investigated the different reactivities of airway smooth muscles to volatile anesthetics by measuring porcine tracheal or bronchial (third to fifth generation) smooth muscle tension and intracellular concentration of free Ca2+ ([Ca2+]i) and by measuring inward Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDCs). METHODS: Intracellular concentration of free Ca2+ was monitored by the 500-nm light emission ratio of Ca2+ indicator fura-2. Isometric tension was measured simultaneously. Whole-cell patch clamp recording techniques were used to investigate the effects of volatile anesthetics on ICa in dispersed smooth muscle cells. Isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) was introduced into a bath solution. RESULTS: The volatile anesthetics tested had greater inhibitory effects on carbachol-induced bronchial smooth muscle contraction than on tracheal smooth muscle contraction. These inhibitory effects by the anesthetics on muscle tension were parallel to the inhibitory effects on [Ca2+]i. Although tracheal smooth muscle cells had only L-type VDCs, some bronchial smooth muscle cells (approximately 30%) included T-type VDC. Each of the two anesthetics significantly inhibited the activities of both types of VDCs in a dose-dependent manner; however, the anesthetics had greater inhibitory effects on T-type VDC activity in bronchial smooth muscle. CONCLUSIONS: The existence of the T-type VDC in bronchial smooth muscle and the high sensitivity of this channel to volatile anesthetics seem to be, at least in part, responsible for the different reactivities to the anesthetics in tracheal and bronchial smooth muscles.

Anesthetics, Inhalation↗

PubMed2001

Role of c-Src in the regulation of vascular contraction and Ca2+ signaling by angiotensin II in human vascular smooth muscle cells.

OBJECTIVE: Tyrosine kinases, typically associated with growth-signaling pathways, also play a role in Ang II-stimulated vascular contraction. However the specific kinases involved are unclear. We hypothesize here that c-Src, a non-receptor tyrosine kinase, is an important upstream regulator of vascular smooth muscle cell (VSMC) Ca2+ signaling and associated vascular contraction induced by Ang II. METHODS: Cultured VSMCs from resistance arteries of healthy subjects were studied. Human VSMCs electroporated with anti-c-Src antibody and c-Src-deficient VSMCs from small arteries of c-Src knockout mice (Src-/-mVSMCs) were also investigated. Intracellular free Ca2+ concentration ([Ca2+]i), c-Src activity and IP3 production were measured by fura 2, immunoblot and radioimmunoassay respectively. Contraction was examined in intact rat small arteries. RESULTS: Ang II rapidly increased VSMC c-Src activity, with peak responses obtained at 1 min. Ang II induced a biphasic [Ca2+]i response (Emax = 636 +/- 123 nmol/l). The initial [Ca2+]i transient, mediated primarily by Ca2+mobilization, was dose-dependently attenuated by the selective Src inhibitor, PP2, but not by PP3 (inactive analogue). Ang II-elicited [Ca2+]i responses were blunted in cells electroporated with anti-c-Src antibodies and in c-Src-/-mVSMCs. Src inhibition decreased Ang II-induced generation of IP3 in human VSMCs. Ang II dose-dependently increased vascular contraction (Emax = 40 +/- 6.5%). These responses were attenuated by PP2 (Emax = 7.8 +/- 0.08%) but not by PP3 (Emax = 35 +/- 4.5%). CONCLUSIONS: Our findings identify c-Src as an important regulator of VSMC [Ca2+]i signaling and implicate a novel contractile role for this non-receptor tyrosine kinase in Ang II-stimulated vascular smooth muscle.

Angiotensin II↗

PubMed2001

Involvement of Ca2+ -activated K+ channels in ginsenosides-induced aortic relaxation in rats.

Ginsenosides (GS), an extract of Panax ginseng, have been reported to be effective in inducing vascular relaxation mediated by nitric oxide (NO) release. The present experiments were designed to determine whether this GS-induced vasorelaxation also involves Ca2+ -activated K+ (KCa) channels in vascular smooth muscle cells (VSMC) in addition to endothelium-derived NO. GS induced vasorelaxation in rat aortic rings, which had been precontracted with phenylephrine, in a concentration-dependent manner. This GS-induced relaxation was partially reversed by tetraethylammonium (TEA), an inhibitor of KCa channels; methylene blue (MB), an inhibitor of soluble guanylate cyclase; as well as Nomega-nitro-L-arginine (L-NNA), but not by glybenclamide. In cultured VSMC and endothelial cells, KCa channels were activated by GS. This action was abolished by TEA, but was not blocked by glybenclamide. In addition, the GS-induced activity of KCa channels was partially inhibited by MB or H-8. These results indicate that the activation of KCa channels involved, at least in part, the GS-induced vasorelaxation of rat aorta.

Analgesics↗

PubMed2001

Flexible use of high-density oligonucleotide arrays for single-nucleotide polymorphism discovery and validation.

A method for identifying and validating single nucleotide polymorphisms (SNPs) with high-density oligonucleotide arrays without the need for locus-specific polymerase chain reactions (PCR) is described in this report. Genomic DNAs were divided into subsets with complexity of ~10 Mb by restriction enzyme digestion and gel-based fragment size resolution, ligated to a common adaptor, and amplified with one primer in a single PCR reaction. As a demonstration of this approach, a total of 124 SNPs were located in 190 kb of genomic sequences distributed across the entire human genome by hybridizing to high-density variant detection arrays (VDA). A set of independent validation experiments was conducted for these SNPs employing bead-based affinity selection followed by hybridization of the affinity-selected SNP-containing fragments to the same VDA that was used to identify the SNPs. A total of 98.7% (74/75) of these SNPs were confirmed using both DNA dideoxynucleotide sequencing and the VDA methodologies. With flexible sample preparation, high-density oligonucleotide arrays can be tailored for even larger scale genome-wide SNP discovery as well as validation.

Cell Line↗

PubMed2001

Evolutionarily conserved sequences on human chromosome 21.

Comparison of human sequences with the DNA of other mammals is an excellent means of identifying functional elements in the human genome. Here we describe the utility of high-density oligonucleotide arrays as a rapid approach for comparing human sequences with the DNA of multiple species whose sequences are not presently available. High-density arrays representing approximately 22.5 Mb of nonrepetitive human chromosome 21 sequence were synthesized and then hybridized with mouse and dog DNA to identify sequences conserved between humans and mice (human-mouse elements) and between humans and dogs (human-dog elements). Our data show that sequence comparison of multiple species provides a powerful empiric method for identifying actively conserved elements in the human genome. A large fraction of these evolutionarily conserved elements are present in regions on chromosome 21 that do not encode known genes.

Animals↗