elastin and Chromosome-Deletion

Research into phenotype-genotype correlations in neurodevelopmental disorders has greatly elucidated the contribution of genetic and neurobiological factors to variations in typical and atypical development. Etiologically relatively homogeneous disorders, such as Williams syndrome (WS), provide unique opportunities for elucidating gene-brain-behavior relationships. WS is a neurogenetic disorder caused by a hemizygous deletion of approximately 25 genes on chromosome 7q11.23. This results in a cascade of physical, cognitive-behavioral, affective, and neurobiological aberrations. WS is associated with a markedly uneven neurocognitive profile, and the mature state cognitive profile of WS is relatively well developed. Although anecdotally, individuals with WS have been frequently described as unusually friendly and sociable, personality remains a considerably less well studied area. This paper investigates genetic influences, cognitive-behavioral characteristics, aberrations in brain structure and function, and environmental and biological variables that influence the social outcomes of individuals with WS. We bring together a series of findings across multiple levels of scientific enquiry to examine the social phenotype in WS, reflecting the journey from gene to the brain to behavior. Understanding the complex multilevel scientific perspective in WS has implications for understanding typical social development by identifying important developmental events and markers, as well as helping to define the boundaries of psychopathology.

Topics: Adolescent; Adult; Brain; Child; Child, Preschool; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 7; Cognition Disorders; Cross-Cultural Comparison; Elastin; Emotions; Female; Genotype; Humans; Infant; Intellectual Disability; Magnetic Resonance Imaging; Male; Personal Construct Theory; Personality Development; Phenotype; Social Environment; Williams Syndrome

Topics: Adult; Cardiovascular Diseases; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 7; Cytogenetic Analysis; Elastin; Female; Humans; Male; Prognosis; Williams Syndrome

Topics: Chromosome Deletion; Chromosomes, Human, Pair 7; Diagnosis, Differential; DNA-Binding Proteins; Elastin; Genes, Dominant; Humans; Lim Kinases; Prognosis; Protein Kinases; Protein Serine-Threonine Kinases; Williams Syndrome

Supravalvular aortic stenosis (SVAS) occurs as an autosomal dominant trait or as part of the phenotype of the usually sporadic condition Williams syndrome. SVAS is the result of mutation or deletion of the elastin gene (ELN), located at chromosome 7q11.23. Thus, SVAS may be more appropriately termed an elastin arteriopathy. Studies have demonstrated various point mutations and intragenic deletions of ELN resulting in nonsyndromic SVAS. Individuals with Williams syndrome are hemizygous for the elastin gene, owing to a 1 to 2 megabase deletion of a portion of the long arm of chromosome 7 that encompasses ELN. This submicroscopic deletion is readily detected by fluorescent in-situ hybridization, useful in the diagnosis of Williams syndrome. The severity of SVAS is quite variable, both in series of Williams syndrome patients and within SVAS kindreds, suggesting that other genetic factors are involved in expression of the phenotype. Experiments with elastin knockout mice will likely yield clues regarding the role of elastin in arterial morphogenesis and the pathogenesis of obstructive vascular disease.

Topics: Animals; Aortic Valve Stenosis; Chromosome Aberrations; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 7; DNA Mutational Analysis; Elastin; Gene Expression; Genes, Dominant; Humans; Mice; Phenotype; Williams Syndrome

Topics: Attention; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Chromosome Deletion; Chromosomes, Human, Pair 7; Dose-Response Relationship, Drug; Double-Blind Method; Elastin; Humans; Male; Methylphenidate; Williams Syndrome

Williams-Beurens syndrome (WBS) is a rare genetic disorder caused by a recurrent 7q11.23 microdeletion. Clinical characteristics include typical facial dysmorphisms, weakness of connective tissue, short stature, mild to moderate intellectual disability and distinct behavioral phenotype. Cardiovascular diseases are common due to haploinsufficiency of ELN gene. A few cases of larger or smaller deletions have been reported spanning towards the centromeric or the telomeric regions, most of which included ELN gene. We report on three patients from two unrelated families, presenting with distinctive WBS features, harboring an atypical distal deletion excluding ELN gene. Our study supports a critical role of CLIP2, GTF2IRD1, and GTF2I gene in the WBS neurobehavioral profile and in craniofacial features, highlights a possible role of HIP1 in the autism spectrum disorder, and delineates a subgroup of WBS individuals with an atypical distal deletion not associated to an increased risk of cardiovascular defects.

Topics: Adolescent; Adult; Celiac Disease; Child; Chromosome Deletion; Chromosomes, Human, Pair 7; Elastin; Female; Genetic Predisposition to Disease; Haploinsufficiency; Humans; Neurocognitive Disorders; Phenotype; Williams Syndrome

The voice of persons with Williams syndrome (WS) is described as hoarse with a deep and unstable fundamental frequency (f0). These observations may be justified by the deficit of elastin due to a haplo-insufficiency in the ELN gene characteristic of the syndrome. In view of the possible relationship between elastin deficit and dysphonia, a study of the dynamic function of WS phonation was conducted by means of biomechanical analysis. In order to assess the presence of dysphonic symptoms and their degree of severity, the biomechanical description of WS phonation has been evaluated in terms of dynamic mass and viscoelasticity estimates. Glottal biomechanical features such as vocal fold dynamic mass, stiffness, unbalances, and laryngeal tremor of 12 children with WS aged 3 to 8 years (five girls and seven boys) have been estimated and compared with the normative phonation of 97 children with typical development (53 girls and 44 boys). The results show that WS children show differences in f0, vocal fold mass and stiffness, phonation stability, glottal contact defects, and laryngeal tremor. The conclusions may help to make a more complete view of the connection between WS and dysphonia based on objective assessments.

Topics: Acoustics; Age Factors; Biomechanical Phenomena; Case-Control Studies; Child; Child, Preschool; Chromosome Deletion; Elastin; Female; Humans; Larynx; Male; Phonation; Speech Production Measurement; Voice Disorders; Voice Quality; Williams Syndrome

Williams-Beuren syndrome (WBS) is a chromosomal microdeletion syndrome typically presenting with intellectual disability, a unique personality, a characteristic facial appearance, and cardiovascular disease. Several clinical features of WBS are thought to be due to haploinsufficiency of elastin (ELN), as the ELN locus is included within the WBS critical region at 7q11.23. Emphysema, a disease attributed to destruction of pulmonary elastic fibers, has been reported in patients without WBS who have pathogenic variants in ELN but only once (in one patient) in WBS. Here we report a second adult WBS patient with emphysema where the diagnosis of WBS was established subsequent to the discovery of severe bullous emphysema. Haploinsufficiency of ELN likely contributed to this pulmonary manifestation of WBS. This case emphasizes the contribution of rare genetic variation in cases of severe emphysema and provides further evidence that emphysema should be considered in patients with WBS who have respiratory symptoms, as it may be under-recognized in this patient population.

Topics: Chromosome Deletion; Chromosomes, Human, Pair 7; Elastin; Genetic Variation; Haploinsufficiency; Humans; In Situ Hybridization, Fluorescence; Male; Middle Aged; Phenotype; Pulmonary Emphysema; Williams Syndrome

This study assessed the prevalence of scoliosis and the patterns of scoliotic curves in patients with Williams-Beuren syndrome. Williams-Beuren syndrome is caused by a chromosome 7q11.23 deletion in a region containing 28 genes, with the gene encoding elastin situated approximately at the midpoint of the deletion. Mutation of the elastin gene leads to phenotypic changes in patients, including neurodevelopmental impairment of varying degrees, characteristic facies, cardiovascular abnormalities, hypercalcemia, urological dysfunctions, and bone and joint dysfunctions.. A total of 41 patients diagnosed with Williams-Beuren syndrome, who were followed up at the genetics ambulatory center of a large referral hospital, were included in the study. There were 25 male subjects. The patients were examined and submitted to radiographic investigation for Cobb angle calculation.. It was observed that 14 patients had scoliosis; of these 14 patients, 10 were male. The pattern of deformity in younger patients was that of flexible and simple curves, although adults presented with double and triple curves. Statistical analysis showed no relationships between scoliosis and age or sex.. This study revealed a prevalence of scoliosis in patients with Williams-Beuren syndrome of 34.1%; however, age and sex were not significantly associated with scoliosis or with the severity of the curves.

Topics: Adolescent; Adult; Age Factors; Brazil; Child; Child, Preschool; Chromosome Deletion; Cross-Sectional Studies; Elastin; Female; Humans; Male; Multivariate Analysis; Prevalence; Scoliosis; Sex Factors; Williams Syndrome; Young Adult

Williams-Beuren syndrome (WBS) is a genetic disorder characterized by physical and intellectual developmental delay, associated with congenital heart disease and facial dysmorphism. WBS is caused by a microdeletion on chromosome 7 (7q11.23), which encompasses the elastin (ELN) gene and about 27 other genes. The gold standard for WBS laboratory diagnosis is FISH (fluorescence in situ hybridization), which is very costly. As a possible alternative, we investigated the accuracy of three clinical diagnostic scoring systems in 250 patients with WBS diagnosed by FISH. We concluded that all three systems could be used for the clinical diagnosis of WBS, but they all gave a low percentage of false-positive (6.0-9.2%) and false-negative (0.8-4.0%) results. Therefore, their use should be associated with FISH testing.

Topics: Chromosome Deletion; Chromosomes, Human, Pair 7; Elastin; Female; Humans; In Situ Hybridization, Fluorescence; Male; Research Design; Williams Syndrome

The Williams-Beuren syndrome (WBS) is a genetic disorder caused by a heterozygous ~1.5-Mb deletion. The aim of this study was to determine how the genetic changes in a Wbs mouse model alter Eln expression, blood pressure, vessel structure, and abdominal aortic wall dynamics in vivo.. Elastin (ELN) transcript levels were quantified by qRT-PCR and blood pressure was measured with a tail cuff system. M-mode ultrasound was used to track pulsatile abdominal aortic wall motion. Aortas were sectioned and stained to determine medial lamellar structure.. ELN transcript levels were reduced by 38-41% in Wbs mice lacking one copy of the ELN gene. These mice also had a 10-20% increase in mean blood pressure and significantly reduced circumferential cyclic strain (p < 0.001). Finally, histological sections showed disorganized and fragmented elastin sheets in Wbs mice, but not the characteristic increase in lamellar units seen in Eln(+/-) mice.. The deletion of Eln in this Wbs mouse model results in lower gene expression, hypertension, reduced cyclic strain, and fragmented elastin sheets. The observation that the number of medial lamellar units is normal in Wbs deletion mice, which is in contrast to Eln(+/-) mice, suggests other genes may be involved in vascular development.

Topics: Animals; Aorta, Abdominal; Blood Pressure; Cardiovascular Abnormalities; Chromosome Deletion; Disease Models, Animal; Elasticity; Elastin; Female; Gene Expression; Male; Mice; Mice, Inbred C57BL; Phenotype; Ultrasonography; Williams Syndrome

Williams-Beuren syndrome (WBS) is caused by a submicroscopic deletion on chromosome 7q11.23 that encompasses the entire elastin (ELN) gene. Elastin, a key component of elastic fibers within the lung, is progressively destroyed in emphysema. Defects in the elastin gene have been associated with increased susceptibility towards developing chronic obstructive pulmonary disease (COPD) and emphysema in both humans and mice. We postulate that hemizygosity at the elastin gene locus may increase susceptibility towards the development of COPD and emphysema in subjects with WBS. We describe an adult subject with WBS who was a lifelong non-smoker and was found to have moderate emphysema. We also examined the pulmonary function of a separate cohort of adolescents and young adults with WBS. Although no significant spirometric abnormalities were identified, a significant proportion of subjects reported respiratory symptoms. Thus, while significant obstructive disease does not appear to be common in relatively young adults with WBS, subclinical emphysema and lung disease may exist which possibly could worsen with advancing age. Further investigation may elucidate the pathogenesis of non-smoking-related emphysema.

Topics: Adolescent; Adult; Animals; Case-Control Studies; Chromosome Deletion; Chromosomes, Human, Pair 7; Elastin; Female; Humans; Male; Mice; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Respiratory Function Tests; Williams Syndrome; Young Adult

Topics: Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 7; Coronary Stenosis; Coronary Vessels; Elastin; Humans; Male; Ultrasonography; Williams Syndrome

Williams syndrome (WS) is a neurodevelopmental disorder caused by a deletion in the 7q11.23 region which includes at least 17 genes. The presence of autistic features in WS is a controversial issue. While some authors describe WS as the opposite phenotype of autism, recent studies indicate that both share many common characteristics. We report a 12-year-old boy diagnosed as autistic disorder and WS with hemizygosity at the elastin locus and a karyotype of 46,XY,del(7)(q11.21q11.23). Molecular genetic studies have shown that deletion at the elastin gene may account for the cardiovascular abnormalities seen in WS, but autistic features are likely caused by other genes flanking elastin.

Topics: Autistic Disorder; Child; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 7; Diagnosis, Differential; Elastin; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Male; Phenotype; Williams Syndrome

Topics: Abnormalities, Multiple; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 7; Elastin; Female; Gene Deletion; Humans; Male; Microsatellite Repeats; Pedigree; Spasm; Syndrome; Williams Syndrome

Williams syndrome (WS) is a rare genetic disorder involving a characteristic cardiac defect, typical facial appearance, and an uneven profile of cognitive strengths and weaknesses. WS is caused by a hemizygous deletion in chromosome band 7q11.23, including the gene for elastin (ELN). Typically, individuals with WS seem driven to greet and interact with strangers. The goal of the present study was to investigate age-related changes in the expression of hypersociability in WS. Parents of 64 children with WS, 31 children with Down syndrome (DS), and 27 normal controls (NC) provided data concerning specific aspects of their children's social behavior using the Salk Institute Sociability Questionnaire (SISQ). Children ranged in age from 1 year, 1 month to 12 years, 10 months. Consistent with earlier findings, whole group analyses showed the WS group to be significantly higher on all aspects of sociability studied. Comparisons among the groups at different ages revealed that hypersociability is evident even among very young children with WS, and, significantly, children with WS exceed children with DS with respect to Global Sociability and Approach Strangers in every age group. The findings from children who have the typical deletion for WS are contrasted with data obtained from a young child with WS who has a smaller deletion and many physical features of WS, but who does not demonstrate hypersociability, providing intriguing clues to a genetic basis of social behavior in this syndrome. These data suggest the involvement of a genetic predisposition in the expression of hypersociability in WS.

Topics: Age Factors; Analysis of Variance; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 7; Down Syndrome; Elastin; Family Health; Female; Genotype; Humans; Infant; Male; Social Behavior; Surveys and Questionnaires; Williams Syndrome

As the largest interhemispheric commissure in the brain, the corpus callosum is of particular interest in disorders that may preferentially affect white matter development such as Williams syndrome (WS). Individuals with WS possess a remarkable array of neurobehavioral peaks and valleys, including deficits in visuospatial ability, mathematics, and attention, but with relative preservation of language and affect. Our study measured the corpus callosum and its primary subdivisions using high-resolution MRI in 20 individuals with WS (13 females and seven males; mean age 28.5, SD 8.3 years; range 19 to 44 years) and 20 age- and sex-matched control participants (mean age 28.5, SD 8.2 years; range 19 to 48 years). Total midsagittal corpus callosum area was reduced (F=4.5, p=0.04, df=36) in the WS population. The area of the splenium (F=12.4, p=0.001, df=36) and isthmus (F=9.4, p=0.004, df=36) were disproportionately reduced in WS beyond the absolute reduction of the entire corpus callosum. These reductions are in concordance with other neuroanatomical findings of decreased parietooccipital volumes as well as the observed visuospatial problems associated with WS.

Topics: Adult; Chromosome Deletion; Corpus Callosum; Elastin; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Orientation; Problem Solving; Psychomotor Performance; Reference Values; Williams Syndrome

Major chromosome abnormalities are present in 0.65% of all neonates. Fluorescent in situ hybridization (FISH) is useful in diagnosing microdeletion syndromes that would otherwise be difficult to diagnose using standard cytogenetics. In this study, we used FISH analysis in the laboratory diagnosis of 4 patients with Prader-Willi Syndrome [del(15)(q11.2q12)], 4 patients with DiGeorge syndrome [del(22)(q11.2q11.23)] and 4 patients with Williams syndrome [del(7)(q11.23q11.23)]. High-resolution chromosome analysis in all these patients was either normal or inconclusive but all the syndromes were confirmed using FISH. We recommend cytogenetic analysis should always be supplemented with FISH to diagnose all cases suspected of a microdeletion syndrome.

Topics: Adolescent; Child, Preschool; Chromosome Deletion; Cytogenetic Analysis; Diagnosis, Differential; DiGeorge Syndrome; Elastin; Humans; In Situ Hybridization, Fluorescence; Infant; Karyotyping; Metaphase; Phenotype; Prader-Willi Syndrome; Sensitivity and Specificity; Williams Syndrome

Williams syndrome (WS) is associated with a submicroscopic deletion of the elastin gene (ELN) at 7q11.23. The deletion encompasses closely linked DNA markers. We have investigated 44 patients referred for possible WS using fluorescence in situ hybridization (FISH) analysis with a P1 clone containing an insert from the ELN, as well as performing genotype analysis of patients and parents with four DNA polymorphisms. Twenty-four patients were found to have deletions, 19 of whom were found clinically to have typical WS. The facial features were especially characteristic. None of the patients without detectable deletions was reported to have typical WS features, although one had supravalvular aortic stenosis, hypercalcemia, and mental retardation. No evidence was found in this material for variability of the size of the deletion. Our study supports the usefulness of analysis of ELN deletion in WS patients, both for confirmation of diagnosis and for genetic counselling.

Topics: Adolescent; Adult; Child; Child, Preschool; Chromosome Banding; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 7; Dinucleotide Repeats; DNA; Elastin; Female; Gene Deletion; Humans; In Situ Hybridization, Fluorescence; Infant; Karyotyping; Male; Polymorphism, Genetic; Williams Syndrome

Williams syndrome (WS) is characterized by distinct facial changes, growth deficiency, mental retardation, and congenital heart defect (particularly supravalvular aortic stenosis), associated at times with infantile hypercalcemia. Molecular genetic studies have indicated that hemizygosity at the elastin locus (7q11.23) causes WS. The purpose of this study was to confirm that this regional deletion, involving the elastin locus, is the cause of WS in Japan, and to clarify the correlation between the phenotype and the elastin locus. Thirty-two patients with WS and thirty of their relatives were examined by fluorescent in situ hybridization (FISH), using the WS chromosome region (WSCR) probe. All patients had cardiovascular disease (100%), 30 had typical WS facial changes (94%), 31 had mental retardation or developmental delay (97%), 16 were small-for-date at birth (50%), 14 had short stature (44%), and 13 had dental anomalies (41%). No relatives showed any manifestation of WS. Hemizygosity for a region of 7q11.23, involving the elastin locus, was found in all WS patients, but was not found in the 30 relatives.

Topics: Adolescent; Adult; Angiocardiography; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 7; DNA Probes; Elastin; Female; Humans; In Situ Hybridization; Infant; Male; Williams Syndrome

Fluorescence in situ hybridisation (FISH) and conventional chromosome analysis were performed on a series of 52 patients with classical Williams-Beuren syndrome (WBS), suspected WBS, or supravalvular aortic stenosis (SVAS). In the classical WBS group, 22/23 (96%) had a submicroscopic deletion of the elastin locus on chromosome 7, but the remaining patient had a unique interstitial deletion of chromosome 11 (del(11)(q13.5q14.2)). In the suspected WBS group 2/22 (9%) patients had elastin deletions but a third patient had a complex karyotype including a ring chromosome 22 with a deletion of the long arm (r(22)(p11-->q13)). In the SVAS group, 1/7 (14%) had an elastin gene deletion, despite having normal development and minimal signs of WBS. Overall, some patients with submicroscopic elastin deletions have fewer features of Williams-Beuren syndrome than those with other cytogenetic abnormalities. These results, therefore, emphasise the importance of a combined conventional and molecular cytogenetic approach to diagnosis and suggest that the degree to which submicroscopic deletions of chromosome 7 extend beyond the elastin locus may explain some of the phenotypic variability found in Williams-Beuren syndrome.

Topics: Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 7; Elastin; Female; Gene Deletion; Genetic Variation; Genotype; Humans; In Situ Hybridization, Fluorescence; Infant; Male; Phenotype; Pulmonary Valve Stenosis; Ring Chromosomes; Williams Syndrome

To correlate presence or absence of a 7q11 microdeletion with the clinical picture of the Williams-Beuren syndrome (WBS), we investigated 29 patients with a clinical diagnosis of WBS or WBS-like features, aged 1-30 years, using molecular analysis and/or fluorescent in situ hybridization (FISH). Deletions at 7q11 were found in 75% of the patients (22 out of 29). Nine deletions occurred on a paternal, and ten on a maternal chromosome; three deletions were demonstrated by FISH only, and parental origin could thus not be determined. All deletion patients aged between 2 years and puberty displayed a distinct pattern of facial features (including periorbital fullness, short nose with flat bridge, wide mouth, and full lips and cheeks), the characteristic outgoing social behaviour, as well as moderate growth and mental retardation. Two-thirds (15 out of 22) had a cardiovascular malformation, but only one third (7 of 22) had supravalvular aortic stenosis (SVAS). A stellate iris pattern was also present in one-third of the patients only. In the four adult patients with 7q11 deletions, there was prominence of the lower lip whereas fullness of cheeks and periorbital tissue was not seen.. This study confirms that WBS has a unique clinical picture which can be diagnosed clinically, but also shows that the relative frequency of individual features may have been overemphasized in the past, and that a minority of patients may exist who are clinically indistinguishable from WBS but who appear to have no deletion at 7q11.

Topics: Abnormalities, Multiple; Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 7; Developmental Disabilities; Diagnosis, Differential; Elastin; Face; Female; Heart Defects, Congenital; Humans; Infant; Male; Pedigree; Phenotype; Syndrome

The human calcitonin receptor (CTR) is a transmembrane peptide with dual action as a receptor for the hormone calcitonin and as an extracellular calcium sensor. Therefore, CTR dysfunction could lead to disorders of calcium metabolism associated with hypercalcemia, such as the Williams syndrome (WS). WS is a developmental disorder caused by a deletion at chromosome 7q11.23 that includes the elastin locus (ELN). We have mapped the CTR gene (CALCR) to chromosome band 7q21.3 by polymerase chain reaction and single-strand conformation analysis of somatic cell hybrids as well as fluorescence in situ hybridization (FISH) to metaphase chromosome spreads. Two-color FISH cohybridizing CTR and ELN probes confirmed that CALCR maps telomeric to ELN. Subsequent analysis of chromosome spreads from four WS patients revealed deletion of the ELN locus in all of them and normal hybridization of CTR probes to both chromosome 7 homologues, indicating that CALCR lies outside the deleted region.

Topics: Animals; Base Sequence; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 7; Cricetinae; Cricetulus; DNA Primers; Elastin; Genomic Library; Growth Disorders; Humans; Hybrid Cells; In Situ Hybridization, Fluorescence; Molecular Sequence Data; Receptors, Calcitonin; Syndrome

To delineate cis-acting regulatory elements of the human elastin gene, several elastin promoter region/chloramphenicol acetyltransferase reporter gene constructs were developed. The spectrum of inserts, spanning from -2260 to +2, was shown to contain several SP-1 and AP2 binding sites, as well as putative glucocorticoid, cAMP, and 12-O-tetradecanoylphorbol-13-acetate responsive elements. Assay of promoter activity in transient transfections of rat aortic smooth muscle cells, human skin fibroblasts, HT-1080 human fibrosarcoma cells, HeLa cells, or mouse NIH-3T3 cells allowed delineation of several functional subregions within 2.26 kilobases of the 5'-flanking DNA. The results suggest that the basic promoter element resides within the region -128 to -1, and the 5'-flanking DNA contains several functional regulatory subregions. Also, the regulatory function of three putative SP-1 binding sites was demonstrated by transfections with a plasmid devoid of such sequences. These findings attest to the complexity of transcriptional regulation of the elastin gene.

Topics: Animals; Aorta; Base Sequence; Binding Sites; Chromosome Deletion; Cloning, Molecular; Cyclic AMP; DNA-Binding Proteins; Elastin; Fibroblasts; Fibrosarcoma; Glucocorticoids; HeLa Cells; Humans; Molecular Sequence Data; Muscle, Smooth, Vascular; Plasmids; Polymerase Chain Reaction; Promoter Regions, Genetic; Rats; Regulatory Sequences, Nucleic Acid; Sp1 Transcription Factor; Tetradecanoylphorbol Acetate; Transcription Factors; Transfection; Tumor Cells, Cultured

A comparative analysis of the amino acid and cDNA sequences of bovine elastin a and chick elastin shows that there are considerable differences between these proteins. There is evidence that duplication of segments of DNA and gene rearrangement have occurred in the gene for chick elastin as compared with the gene for bovine elastin. The length of the polypeptide chain of elastin in both species is similar. Therefore, the duplications are compensated for by deletions in the gene for chick elastin.

Topics: Amino Acid Sequence; Animals; Base Sequence; Cattle; Chickens; Chromosome Deletion; DNA; Elastin; Molecular Sequence Data; Multigene Family; Sequence Homology, Nucleic Acid