33 results on '"Jean A. Amos"'
Search Results
2. Developing a Sustainable Process to Provide Quality Control Materials for Genetic Testing
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Daynna J. Wolff, Lawrence M. Silverman, Cecelia S. Hinkel, Patricia Charache, Elisabeth Dequeker, Jeanne C. Beck, Victoria M. Pratt, Elizabeth M. Rohlfs, Lisa V. Kalman, Ann M. Willey, Ira M. Lubin, William Edward Highsmith, Carolyn Sue Richards, David E. Barton, Bin Chen, Emily S. Winn-Deen, Elaine Lyon, Bassem A. Bejjani, Erasmus Schneider, Catherine D. O'Connell, Andrea Ferreira-Gonzalez, D. Joe Boone, Jean A. Amos, Kenneth J. Friedman, Roger V. Lebo, Wayne W. Grody, Daniel H. Farkas, Deborah A. Payne, Benjamin B. Roa, Laurina O. Williams, Michele Caggana, Clark A. Rundell, Dorothy R. Belloni, Maria M. Chan, James C. Willey, Susan H. Bernacki, and Carol L. Greene
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Quality Control ,Government ,Process management ,Quality Assurance, Health Care ,medicine.diagnostic_test ,business.industry ,media_common.quotation_subject ,Control (management) ,Reproducibility of Results ,United States ,Test (assessment) ,Molecular Diagnostic Techniques ,External quality assessment ,Government Regulation ,medicine ,Humans ,Quality (business) ,Professional association ,Genetic Testing ,Centers for Disease Control and Prevention, U.S ,business ,Quality assurance ,Genetics (clinical) ,Genetic testing ,media_common - Abstract
Purpose: To provide a summary of the outcomes of two working conferences organized by the Centers for Disease Control and Prevention (CDC), to develop recommendations for practical, sustainable mechanisms to make quality control (QC) materials available to the genetic testing community. Methods: Participants were selected to include experts in genetic testing and molecular diagnostics from professional organizations, government agencies, industry, laboratories, academic institutions, cell repositories, and proficiency testing (PT)/external Quality Assessment (EQA) programs. Current efforts to develop QC materials for genetic tests were reviewed; key issues and areas of need were identified; and workgroups were formed to address each area of need and to formulate recommendations and next steps. Results: Recommendations were developed toward establishing a sustainable process to improve the availability of appropriate QC materials for genetic testing, with an emphasis on molecular genetic testing as an initial step. Conclusions: Improving the availability of appropriate QC materials is of critical importance for assuring the quality of genetic testing, enhancing performance evaluation and PT/EQA programs, and facilitating new test development. To meet the needs of the rapidly expanding capacity of genetic testing in clinical and public health settings, a comprehensive, coordinated program should be developed. A Genetic Testing Quality Control Materials Program has therefore been established by CDC in March 2005 to serve these needs.
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- 2005
3. Standardization of PCR amplification for fragile X trinucleotide repeat measurements*
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John P. Jakupciak, Catherine D. O’Connell, Kristy L. Richie, Donald H. Atha, and Jean A. Amos
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Repeatability ,Biology ,medicine.disease ,Molecular biology ,DNA sequencing ,law.invention ,Fragile X syndrome ,Capillary electrophoresis ,law ,Gene duplication ,Genetics ,medicine ,Repeated sequence ,Trinucleotide repeat expansion ,Genetics (clinical) ,Polymerase chain reaction - Abstract
To provide the clinical diagnostics community with accurate protocols and measurements for the detection of genetic disorders, we have established a quantitative measurement program for trinucleotide repeats associated with human disease. In this study, we have focused on the triplet repeat associated with fragile X syndrome. Five cell lines obtained from the Coriell Cell Repository were analyzed after polymerase chain reaction (PCR) amplification and size separation. These cell lines were reported to contain CGG repeat elements (ranging from 29 to 110 repeats). Our initial measurements focused on measurement variability: (a) between slab-PAGE and capillary (CE) separation systems (b) interlane variability (slab-PAGE) (c) intergel variability, and (d) variability associated with amplification. Samples were run in triplicate for all measurements, and the analysis performed using Gene Scan analysis software. The repeat sizes were verified by DNA sequence analyzes. The standard deviations for interlane measurements in slab-gels ranged from 0.05 to 0.35. There was also little variation in size measurements performed on different gels and among PCR amplifications. The CGG repeat measurements performed by capillary electrophoresis were more precise, with standard deviations ranging from 0.02 to 0.29. The slab-PAGE and CE size measurements were in agreement except for the pre-mutation alleles, which yielded significantly smaller sizes by CE.
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- 2002
4. Pulmonary Function and Clinical Observations in Men With Congenital Bilateral Absence of the Vas Deferens
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Robert D. Oates, Susan M Sawyer, John E. Mickle, Andrew A. Colin, Aubrey Milunsky, and Jean A. Amos
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Pathology ,Malabsorption ,Cystic Fibrosis ,Genotype ,Respiratory Tract Diseases ,Cystic Fibrosis Transmembrane Conductance Regulator ,Nutritional Status ,Critical Care and Intensive Care Medicine ,Compound heterozygosity ,Gastroenterology ,Cystic fibrosis ,Pulmonary function testing ,Vas Deferens ,Internal medicine ,medicine ,Humans ,Respiratory function ,Sweat ,Polymorphism, Single-Stranded Conformational ,Sweat test ,medicine.diagnostic_test ,business.industry ,Genetic Carrier Screening ,Body Weight ,Respiratory disease ,medicine.disease ,Body Height ,Mutation ,Respiratory Mechanics ,Cardiology and Cardiovascular Medicine ,business - Abstract
Congenital bilateral absence of the vas deferens (CBAVD) was once thought to be a distinct clinical entity, but genetic similarities in men with cystic fibrosis (CF) and CBAVD are described increasingly. We evaluated the clinical status, growth and nutritional state, and respiratory function of 18 men with CBAVD to determine whether these men with different CF transmembrane regulator (CFTR) genotypes may have clinical evidence of mild CF. Following a thorough history and examination, pulmonary function tests, sweat test, and renal ultrasound were performed. Genetic evaluation for 50 known CF mutations, screening for private mutations (single-strand conformational polymorphism and direct sequencing), and assay of the length of the polypyrimidine tract in the splice site acceptor of intron 8 was performed. A history of pulmonary disease was present in three, and an additional man had some features suggestive of malabsorption. Results of general physical examination and anthropomorphic measurements were unremarkable in all patients, with a mean (SD) body mass index of 26 (3). Pulmonary function tests of large and small airway function as well as lung volumes were normal in all except one whose results were consistent with moderate asthma. Five men were compound heterozygotes for CFTR mutations, four of whom had positive sweat tests (sweat chloride >60 mEq/L). Twelve men were heterozygotes for CFTR mutations while no mutations were identified in one man. Although putative etiologic factors may suggest that men with CBAVD and CFTR mutations could be considered within the spectrum of clinical CF, the authors suggest that in men with CBAVD without any other clinical features of CF, the diagnosis of CF may not be made.
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- 1996
5. Aspect de la construction navale à Sulawesi (1969-1999)
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Jean-Claude Amos
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Indonésie ,Sulawesi ,pinisi ,Bugis ,media_common.quotation_subject ,chantiers navals ,construction navale ,Art ,Humanities ,media_common - Abstract
Il y a trente ans, les eaux de l’archipel indonésien étaient labourées de grands voiliers de haute mer évoquant tantôt la grande époque du trafic des épices, tantôt les bateaux de pierre du Borobudur. Il n’en reste plus un seul. Mais les chantiers qui les créèrent, s’adaptant peu ou prou à la motorisation, continuent à lancer des coques à l’ancienne de plus de cent tonneaux. Il y a lieu, avant que cette activité, condamnée à terme, ne perde ses caractères traditionnels, de préciser ou compléter les observations dont elle a déjà été l’objet. Thirty years ago, the waters of the Indonesian Archipelago were furrowed with high sea sailing ships. They evoked one of the great periods of spice trading or the bas-relief stone boats of Borobudur. They have now all disappeared but the building site have, little by little, been adapted to the phenomenon of motorization and the building of hull continues in the ancient way that weight more than 100 tons. Before this activity is condemned to disappear and lose its traditional characteristics, it is important to give more precisions and complete the observation concerning them. Hace treinta años, las aguas del archipiélago indonesio eran recorridos por grandes veleros de alta mar evocando unas veces la gran época del tráfico de las especias, otras veces los barcos de piedra de Borobudur. No queda ninguno. Pero los astilleros que los crearon se adaptan poco a poco a la motorización, y continúan a lanzar cascos como los antiguos de más de cien toneles. Sería necesario precisar o completar las observaciones de las cuales ha sido ya objeto esta actividad antes de que, condenada como está, no pierda sus características tradicionales.
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- 2012
6. Les bateaux vietnamiens dessinés par François-Edmond Paris
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Jean-Claude Amos
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media_common.quotation_subject ,Art ,Humanities ,media_common - Abstract
Au cours de ses trois tours du monde, entre 1826 et 1840, l’enseigne, puis lieutenant de vaisseau Francois-Edmond Pâris a dessine plusieurs centaines d’embarcations exotiques. Il faut replacer dans son contexte la demarche du jeune officier, issu d’un milieu de hauts fonctionnaires et membre d’un corps rarement visite par l’esprit democratique. S’interesser a l’artisanat populaire n’etait pas tres courant a cette epoque ! Le futur amiral ne se contente pas, en effet, d’exploiter le pittoresqu...
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- 2012
7. A mutation in CFTR produces different phenotypes depending on chromosomal background
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C. Davis, J. Mickle, Ronald G. Crystal, David R. Witt, A. E. Shrimpton, Milan Macek, Garry R. Cutting, A. Shuber, Lap-Chee Tsui, Chin-Shyan Chu, C. Graham, W. E. Highsmith, S. M. Cashman, Jean A. Amos, Sheila Curristin, and S. Kiesewetter
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Male ,Mutation rate ,Cystic Fibrosis ,Genotype ,RNA Splicing ,Molecular Sequence Data ,Black People ,Cystic Fibrosis Transmembrane Conductance Regulator ,White People ,Frameshift mutation ,Ethnicity ,Genetics ,Humans ,Suppressor mutation ,Base Sequence ,biology ,Membrane Proteins ,DNA ,Phenotype ,Molecular biology ,Introns ,Cystic fibrosis transmembrane conductance regulator ,Mutation ,RNA splicing ,Mutation (genetic algorithm) ,biology.protein ,Dynamic mutation ,Female - Abstract
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene but the association between mutation (genotype) and disease presentation (phenotype) is not straightforward. We have been investigating whether variants in the CFTR gene that alter splicing efficiency of exon 9 can affect the phenotype produced by a mutation. A missense mutation, R117H, which has been observed in three phenotypes, was found to occur on two chromosome backgrounds with intron 8 variants that have profoundly different effects upon splicing efficiency. A close association is shown between chromosome background of the R117H mutation and phenotype. These findings demonstrate that the genetic context in which a mutation occurs can play a significant role in determining the type of illness produced.
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- 1993
8. Molecular methods and platforms for infectious diseases testing a review of FDA-approved and cleared assays
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Rajyasree, Emmadi, Jerry B, Boonyaratanakornkit, Rangaraj, Selvarangan, Venkatakrishna, Shyamala, Barbara L, Zimmer, Laurina, Williams, Bonita, Bryant, Ted, Schutzbank, Michele M, Schoonmaker, Jean A, Amos Wilson, Leslie, Hall, Preeti, Pancholi, and Kathryn, Bernard
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Molecular Diagnostic Techniques ,Clinical Laboratory Techniques ,Diagnostic Test Approval ,United States Food and Drug Administration ,Humans ,Reagent Kits, Diagnostic ,Review ,Communicable Diseases ,Sensitivity and Specificity ,United States - Abstract
The superior sensitivity and specificity associated with the use of molecular assays has greatly improved the field of infectious disease diagnostics by providing clinicians with results that are both accurate and rapidly obtained. Herein, we review molecularly based infectious disease diagnostic tests that are Food and Drug Administration approved or cleared and commercially available in the United States as of December 31, 2010. We describe specific assays and their performance, as stated in the Food and Drug Administration's Summary of Safety and Effectiveness Data or the Office of In Vitro Diagnostic Device Evaluation and Safety's decision summaries, product inserts, or peer-reviewed literature. We summarize indications for testing, limitations, and challenges related to implementation in a clinical laboratory setting for a wide variety of common pathogens. The information presented in this review will be particularly useful for laboratories that plan to implement or expand their molecular offerings in the near term.
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- 2010
9. Cystic Fibrosis
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Jean A. Amos
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- 2009
10. Genetic Heterogeneity in Tuberous Sclerosis. Study of a Large Collaborative Dataset
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John R.W. Yates, A. E. Fryer, John P. Osborne, L. A. J. Janssen, M. W. Burley, R. S. Kandt, J. Attwood, Margaret A. Pericak-Vance, R. Fahsold, P. M. Conneally, Pamela Flodman, J. A. Trofatter, Marcy C. Speer, Jean A. Amos, M. P. Short, Sue Povey, J. M. Connor, Hope Northrup, Jonathan L. Haines, N. T. Bech-Hansen, D. J. J. Halley, Julian R. Sampson, Ann F. Jewell, and Moyra Smith
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Genetics ,Phenocopy ,Likelihood Functions ,Genetic Linkage ,Genetic heterogeneity ,Chromosomes, Human, Pair 11 ,General Neuroscience ,Chromosome ,Locus (genetics) ,Biology ,medicine.disease ,Penetrance ,General Biochemistry, Genetics and Molecular Biology ,Tuberous sclerosis ,History and Philosophy of Science ,Tuberous Sclerosis ,Genetic linkage ,medicine ,Humans ,Chromosomes, Human, Pair 9 ,Gene ,Polymorphism, Restriction Fragment Length ,Genes, Dominant - Abstract
Tuberous sclerosis (TSC) is a multisystem autosomal dominant hamartosis whose genetics is complicated by reduced penetrance and widely varying clinical expression. Results of linkage analyses have variously suggested two different locations for a TSC gene. A collaborative dataset has been assembled to clarify the issue of genetic heterogeneity. We have now analyzed the data from a combined sample of 111 families. Using Ott's HOMOG programs, we completed three tests of homogeneity: (1) for chromosome 9q, (2) for chromosome 11q, and (3) for the combined 9q and 11q data. For test 1 the chi-square (1 df) was 21.54 (p less than 0.001), for test 2 the chi-square (1 df) was 0.13 (p greater than 0.35), and for test 3 the chi-square (2 df) was 37.61 (p less than 0.0001). Additionally, we examined the combined data for evidence that a third, as yet unlinked locus exists. Results of this last test were suggestive but not significant. Clearly loci for TSC are present on both chromosomes 9q and 11q. The maximum likelihood estimate of the proportion of chromosome 9q-linked families is 0.38, for chromosome 11q-linked families is 0.47, and for the unlinked type 0.15. Alternative explanations for these latter families include chance sampling of recombinants, nongenetic phenocopies, or misclassification.
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- 1991
11. An Attempt to Map Two Genes for Tuberous Sclerosis Using Novel Two-Point Methods
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M. Super, T. Bech-Hansen, J. Attwood, M. W. Burley, Moyra Smith, A. E. Fryer, L. Al-Ghazali, Pamela Flodman, L. A. Sandkuyl, R. Mueller, Jean A. Amos, Jonathan L. Haines, J. H. Edwards, N. E. Morton, M. P. Short, Sue Povey, Julian R. Sampson, Dicky J. J. Halley, John R.W. Yates, John P. Osborne, and L. A. J. Janssen
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Adult ,Likelihood Functions ,Genetic Linkage ,Chromosomes, Human, Pair 11 ,General Neuroscience ,Philosophy ,Chromosome Mapping ,Anatomy ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Tuberous sclerosis ,History and Philosophy of Science ,Tuberous Sclerosis ,medicine ,Humans ,Chromosomes, Human, Pair 9 ,Polymorphism, Restriction Fragment Length - Abstract
Author(s): Povey, S; Attwood, J; Janssen, LA; Burley, M; Smith, M; Flodman, P; Morton, NE; Edwards, JH; Sampson, JR; Yates, JR
- Published
- 1991
12. Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients
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Mark Leppert, Kon Taik Khaw, Bernard Gerrard, Jean A. Amos, Marga Belle White, Claudia Stewart, and Michael Dean
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Adult ,Male ,Cystic Fibrosis ,Molecular Sequence Data ,Biology ,medicine.disease_cause ,Cystic fibrosis ,General Biochemistry, Genetics and Molecular Biology ,Conserved sequence ,Mice ,Xenopus laevis ,Adenosine Triphosphate ,Sequence Homology, Nucleic Acid ,medicine ,Animals ,Humans ,Coding region ,Amino Acid Sequence ,Child ,Peptide sequence ,Genetics ,Mice, Inbred BALB C ,Mutation ,Binding Sites ,Base Sequence ,Point mutation ,Infant, Newborn ,Infant ,DNA ,medicine.disease ,Molecular biology ,Transmembrane protein ,Cystic fibrosis transmembrane conductance regulator ,Pedigree ,Child, Preschool ,biology.protein ,Female ,Carrier Proteins - Abstract
We have identified three different point mutations in the coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Each mutation segregates with the disease in two- or three-generation pedigrees and is not found on the normal chromosome of any documented cystic fibrosis carrier. One of the mutations is found in two independent families that contain at least one individual with a mild course of disease. All of these alterations replace charged amino acids with less polar residues and are found in the putative transmembrane sections of the molecule. The mutated amino acids are found to be conserved in both rodents and amphibians and lie in a region of CFTR that is believed to form a channel in the membrane. Although these alterations are rare, they provide important clues to functionally important regions of the molecule.
- Published
- 1990
13. Cystic Fibrosis
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Eugene H. Lewis, Myra J. Lewis, Jean A. Amos, and Gregory J. Tsongalis
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- 2006
14. Genetically characterized positive control cell lines derived from residual clinical blood samples
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Jeanne C. Beck, Daniel H. Farkas, Elizabeth M. Rohlfs, Michael J. Friez, Thomas W. Prior, Kristy L. Richie, Barbara K. Goodman, Barbara C. Levin, Ana K. Stankovic, Charles M. Strom, Victoria M. Pratt, Feras M. Hantash, Karen Snow-Bailey, Jean A. Amos, Kristin G. Monaghan, Elaine B. Spector, Eugene C. Cole, Antony E. Shrimpton, Frederick V. Schaefer, Susan H. Bernacki, Laurina O. Williams, Timothy T. Stenzel, Catherine A. Stolle, Stephen N. Thibodeau, Kasinathan Muralidharan, and Karla J. Matteson
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medicine.medical_specialty ,Herpesvirus 4, Human ,Clinical Biochemistry ,Population ,Context (language use) ,Biology ,medicine.disease_cause ,Virus ,medicine ,Humans ,Point Mutation ,Genetic Testing ,Lymphocytes ,education ,Molecular Biology ,Genetic testing ,Cell Line, Transformed ,Sequence Deletion ,education.field_of_study ,Mutation ,Blood Specimen Collection ,medicine.diagnostic_test ,Biochemistry (medical) ,Genetic Diseases, Inborn ,Transformation (genetics) ,Peripheral blood lymphocyte ,Immunology ,Medical genetics ,Laboratories - Abstract
Background: Positive control materials for clinical diagnostic molecular genetic testing are in critically short supply. High-quality DNA that closely resembles DNA isolated from patient specimens can be obtained from Epstein–Barr virus (EBV)–transformed peripheral blood lymphocyte cell lines. Here we report the development of a process to (a) recover residual blood samples with clinically important mutations detected during routine medical care, (b) select samples likely to provide viable lymphocytes for EBV transformation, (c) establish stable cell lines and confirm the reported mutation(s), and (d) validate the cell lines for use as positive controls in clinical molecular genetic testing applications.Methods: A network of 32 genetic testing laboratories was established to obtain anonymous, residual clinical samples for transformation and to validate resulting cell lines for use as positive controls. Three panel meetings with experts in molecular genetic testing were held to evaluate results and formulate a process that could function in the context of current common practices in molecular diagnostic testing.Results: Thirteen laboratories submitted a total of 113 residual clinical blood samples with mutations for 14 genetic disorders. Forty-one EBV-transformed cell lines were established. Thirty-five individual point and deletion mutations were shown to be stable after 20 population doublings in culture. Thirty-three cell lines were characterized for specific mutations and validated for use as positive controls in clinical diagnostic applications.Conclusions: A process for producing and validating positive control cell lines from residual clinical blood samples has been developed. Sustainable implementation of the process could help alleviate the current shortage of positive control materials.
- Published
- 2005
15. Carrier screening: a tutorial
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Jean A. Amos and Wayne W. Grody
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Genetics ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Genetic counseling ,Population ,medicine.disease ,Cystic fibrosis ,Cftr gene ,Residual risk ,medicine ,Family history ,Intensive care medicine ,Carrier screening ,education ,business ,Clinical vignette - Abstract
Population carrier screening for cystic fibrosis mutations was launched in the United States in 2001. Despite three years of accrued experience on large numbers of tested couples, many aspects of the testing protocol and the genetic counseling remain problematic, owing to the complexity of the causative CFTR gene, the large number of possible mutations within it, the uncertain genotype–phenotype correlation, and the varying residual risks of a negative test in those with or without a positive family history of the disorder. The clinical vignette presented in this tutorial illustrates many of these issues and the appropriate approach for addressing them. Keywords: cystic fibrosis; genetic screening; carrier screening; genetic counseling; mutation analysis
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- 2005
16. Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: results from a collaborative study
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Weimin Sun, Joy B Redman, W E Highsmith, Victoria M. Pratt, M Friez, Jean A. Amos, Kristin G. Monaghan, Inge M. Buyse, Benjamin B. Roa, Lisa Pike-Buchanan, A L Young, and Charles M. Strom
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Male ,Heterozygote ,Cystic Fibrosis ,Genotype ,Population ,DNA Mutational Analysis ,Cystic Fibrosis Transmembrane Conductance Regulator ,Compound heterozygosity ,Male infertility ,Gene Frequency ,medicine ,Humans ,Allele ,education ,Allele frequency ,Genetics (clinical) ,Genetics ,education.field_of_study ,business.industry ,Heterozygote advantage ,medicine.disease ,Phenotype ,Mutation (genetic algorithm) ,Immunology ,Mutation ,Mutation testing ,Female ,business - Abstract
Purpose: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. Methods: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. Results: Less than 1% of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6% of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). Conclusions: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility. Genet Med 2004:6(5):421–425.
- Published
- 2004
17. Cystic fibrosis
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Myra J. Lewis, Eugene H. Lewis, Jean A. Amos, and Gregory J. Tsongalis
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Cystic Fibrosis ,Liver ,Mutation ,Cystic Fibrosis Transmembrane Conductance Regulator ,Humans ,Lung ,Pancreas ,Bone and Bones - Abstract
On a daily basis, pathologists examine the fundamental basis of human diseases using morphologic, immunologic, and molecular techniques. Cystic fibrosis (CF), as a clinically heterogeneous disease, exemplifies the complex challenges of genetic diseases for the pathologist who attempts to explain the mechanisms of disease and provide rationale for clinical management. This review includes an overview of CF and a discussion of pathophysiologic features and practical components of clinical and anatomic pathology, and concludes with a review of molecular diagnostics.
- Published
- 2004
18. Ca2+-sensitive cytosolic nucleases prevent efficient delivery to the nucleus of injected plasmids
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Gilles Toumaniantz, Denis Escande, Gilles Guihard, Hervé Avet-Loiseau, Jean‐Luc Amos, Jean-Paul Behr, and Hélène Pollard
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DNA, Complementary ,Gene delivery ,Polymerase Chain Reaction ,Cell Line ,Plasmid ,Cytosol ,Complementary DNA ,Drug Discovery ,Genetics ,Animals ,Humans ,Molecular Biology ,Genetics (clinical) ,In Situ Hybridization, Fluorescence ,DNA Primers ,Cell Nucleus ,Nuclease ,biology ,Base Sequence ,Oligonucleotide ,Gene Transfer Techniques ,Transfection ,Molecular biology ,Enzymes ,Biochemistry ,Cytoplasm ,biology.protein ,Molecular Medicine ,Calcium ,Plasmids - Abstract
Background Efficient gene delivery by synthetic vectors is a major challenge in gene therapy. However, inefficient nuclear delivery of cDNA is thought to be a major limiting step in gene transfer using non-viral vectors. It is commonly thought that, in the cytosol, cDNA has to be released from its vector before importation to the nucleus. The stability of naked cDNA in the cytoplasm is not well established. Methods cDNA plasmids, either free or complexed with poly(ethyleneimine) (PEI), were microinjected into the cytoplasm of mammalian cells and their turnover was assessed by fluorescence in situ hybridization (FISH). Incubations of cDNA plasmids in cytosolic extracts were also performed. Results FISH experiments showed that naked cDNA rapidly fade with time when injected into the cytosol. Fading was not observed when naked cDNA plasmids were injected into the nucleus. Incubation of naked cDNA in a cytosolic fraction isolated from mammalian cells reproduced cDNA degradation as observed in microinjection experiments. Nuclease inhibitors, including aurin tricarboxylic acid or Zn2+, prevented in vitro cDNA degradation. The cytosolic nuclease activity was optimal at physiological pH and physiological Ca2+ concentration. By contrast, it was insensitive to Mg2+ or Na+ concentrations. Finally, cDNA complexation with PEI or addition of oligonucleotides prevented in vitro cDNA degradation. Conclusion Altogether, these experiments suggest that cDNA digestion by cytosolic nucleases occur when the decomplexed transgene is present in the cytosol. We propose that the inefficient transfer of cDNA into the nucleus during transfection with synthetic vectors may result from rapid digestion of naked cDNA by a Ca2+-sensitive cytosolic nuclease. Copyright © 2001 John Wiley & Sons, Ltd.
- Published
- 2001
19. 46,XY/47,XYY male with the fragile X syndrome: cytogenetic and molecular studies
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Herman E. Wyandt, Aubrey Milunsky, Xin-Li Huang, Lindsay A. Farrer, Joel Herskowitz, and Jean A. Amos
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Male ,medicine.medical_specialty ,Genetic Linkage ,DNA Mutational Analysis ,Aneuploidy ,Biology ,Cytogenetics ,Y Chromosome ,Genotype ,medicine ,Humans ,Genetics (clinical) ,Sex Chromosome Aberrations ,Southern blot ,Genetics ,Mosaicism ,Infant ,medicine.disease ,Pedigree ,Fragile X syndrome ,Nondisjunction ,Fragile X Syndrome ,Mutation (genetic algorithm) ,Restriction fragment length polymorphism ,Polymorphism, Restriction Fragment Length - Abstract
We report the first case of a 46,XY/47,XYY mosaic male with fragile X[Fra(X)] expression in both cell lines. Cytogenetic analysis, DNA linkage analysis, and direct detection of the pre- and full mutation for the affected individual and his at-risk female relatives were performed. Southern analysis of PstI-digested DNA with probe pX6 clearly distinguished the normal genotype, the premutation, and the full mutation in various individuals in the patient's family. Fra(X) carriers who had normal cytogenetic results were clearly identified by direct mutation analysis. © 1993 Wiley-Liss, Inc.
- Published
- 1993
20. Congenital bilateral absence of the vas deferens and cystic fibrosis. A genetic commonality
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Robert D. Oates and Jean A. Amos
- Subjects
Male ,Heterozygote ,Pancreatic disease ,Cystic Fibrosis ,Genetic Linkage ,Urology ,Genetic counseling ,Genetic Counseling ,Gene mutation ,Bioinformatics ,medicine.disease_cause ,Cystic fibrosis ,Vas Deferens ,Gene duplication ,medicine ,Humans ,Genetic Testing ,ΔF508 ,Genetic testing ,Mutation ,medicine.diagnostic_test ,business.industry ,Homozygote ,Gene Amplification ,medicine.disease ,Pedigree ,business - Abstract
CF and CBAVD are really just ends of a clinical spectrum. The type and nature of the mutations in the CF gene probably determine the phenotypic expression of the patient. Perhaps all patients homozygous for delta F508, for example, will have severe pulmonary and pancreatic disease as well as absent vasa, whereas those with other combinations, such as delta F508/D1270N, will be unaffected in terms of pulmonary and pancreatic function but will have absent vasa. Besides contributing to a better understanding of the nature of CBAVD, this linkage of CF and CBAVD most importantly mandates genetic screening and counseling for appropriate family members and even the patient's spouse. In addition, a broader understanding of CF is now at hand, as this brings a whole new cohort of patients under the CF umbrella. Many of these will have at least one, if not two, rare or novel CF gene mutations. Once all of these mutations have been detected and defined, our knowledge of the CF gene, its mutations, and their implications will be dramatically expanded.
- Published
- 1993
21. A 22-bp deletion in the coding region of the cystic fibrosis gene
- Author
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Marga Belle White, Michael Dean, Aubrey Milunsky, Bernard Gerrard, and Jean A. Amos
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Adult ,Male ,Pancreatic disease ,Cystic Fibrosis ,Molecular Sequence Data ,Cystic Fibrosis Transmembrane Conductance Regulator ,DNA, Single-Stranded ,Biology ,medicine.disease_cause ,Cystic fibrosis ,Exon ,Genetics ,medicine ,Coding region ,Humans ,Amino Acid Sequence ,Peptide sequence ,Mutation ,Base Sequence ,Membrane Proteins ,medicine.disease ,Cystic fibrosis transmembrane conductance regulator ,Membrane protein ,Cancer research ,biology.protein ,Nucleic Acid Conformation ,Chromosome Deletion - Published
- 1992
22. Genetic Analysis of Ion Transport
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Gianfranco Sebastio, V. Baranov, Mark Leppert, B. Gerrard, M. Ianuzzi, Jean A. Amos, N. Kapronov, M. Dean, Marga Belle White, and L. Krueger
- Subjects
Cystic fibrosis gene ,biology ,Sodium ,chemistry.chemical_element ,medicine.disease ,Cystic fibrosis ,Chloride ,Genetic analysis ,Molecular biology ,Cystic fibrosis transmembrane conductance regulator ,chemistry ,medicine ,Chloride channel ,biology.protein ,Ion transporter ,medicine.drug - Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder, and di Sant’ Agnese et al. [3] found that the sweat of CF patients contains an excess of sodium and chloride ions. Defects in the regulation of chloride ion transport have been documented in CF epithelial cells [5, 10, 14, 16]. The chloride channel normally responds to β-adrenergic agents, but CF cells are defective in this response [6, 9,14]. It has been proposed that the CF defect involves a pathway whereby cAMP regulates ion transport.
- Published
- 1992
23. The value of deletion analysis for carrier detection in Duchenne muscular dystrophy (DMD)
- Author
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Jean A. Amos, Paula Finn, Bassem Bejjani, and Aubrey Milunsky
- Subjects
musculoskeletal diseases ,Adult ,Genetic Linkage ,Genetic counseling ,Duchenne muscular dystrophy ,Genetic Carrier Screening ,Prenatal diagnosis ,Genetic Counseling ,Paternity ,Carrier testing ,Genetic analysis ,Muscular Dystrophies ,Genetic linkage ,Pregnancy ,Risk Factors ,Prenatal Diagnosis ,Genetics ,medicine ,Humans ,Genetics (clinical) ,Linkage (software) ,business.industry ,Chromosome Mapping ,medicine.disease ,Pedigree ,Female ,Chromosome Deletion ,business - Abstract
We performed genetic analysis for carrier detection for several at-risk females in a four-generation Duchenne muscular dystrophy (DMD) pedigree using deletion analysis. We demonstrated that dosage analysis is a suitable alternative method to determine the carrier status of female relatives of DMD patients shown to have a deletion within the DMD gene. Subsequently, we diagnosed an affected male fetus for an at-risk female shown to be a DMD carrier by deletion analysis. The usefulness of deletion and linkage analysis are compared. In this family, linkage analysis was complicated by the unavailability of key family members, two recombination events and by previously undisclosed nonpaternity. We found that dosage analysis was more efficient than linkage for carrier evaluation in this family.
- Published
- 1991
24. Prenatal diagnosis of myotonic muscular dystrophy with linked deoxyribonucleic acid probes
- Author
-
Aubrey Milunsky, Jeff M. Milunsky, James Skare, Thomas A. Maher, and Jean A. Amos
- Subjects
musculoskeletal diseases ,Fetus ,medicine.medical_specialty ,Pediatrics ,business.industry ,Cytogenetics ,Obstetrics and Gynecology ,Prenatal diagnosis ,Endocrinology ,In utero ,Myotonic muscular dystrophy ,Pregnancy ,Internal medicine ,Prenatal Diagnosis ,medicine ,Humans ,Myotonic Dystrophy ,Female ,Family history ,business ,DNA Probes - Abstract
Since the localization of the myotonic muscular dystrophy gene, closer deoxyribonucleic acid markers have been discovered. These now facilitate both presymptomatic and prenatal diagnosis of myotonic muscular dystrophy. We report our prenatal diagnosis experience with six cases in five families. Obstetricians are advised to inform their patients with a family history of myotonic muscular dystrophy of these testing opportunities. The fetus of the mother with myotonic muscular dystrophy who remains in utero until term is at considerable risk, as is the mother herself, of serious obstetric complications.
- Published
- 1991
25. Identification of Cystic Fibrosis Mutations
- Author
-
Mark Leppert, V S Baranov, Bernard Gerrard, Leslie J. Krueger, Claudia Stewart, Douglas S. Holsclaw, Jean A. Amos, Marga Belle White, Michael Dean, Nicolai I. Kapronov, and Lynne M. Quittell
- Subjects
Mutation ,biology ,medicine.disease ,medicine.disease_cause ,Cystic fibrosis ,Molecular biology ,Cystic fibrosis transmembrane conductance regulator ,law.invention ,Exon ,chemistry.chemical_compound ,chemistry ,law ,Genotype ,medicine ,biology.protein ,Gene ,Polymerase chain reaction ,DNA - Abstract
Using oligonucleotide primers from the sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene we have employed the polymerase chain reaction to amplify several coding exons. These regions have been examined from 110 patients that contain 127 chromosomes without the common CF mutation (DeltaF508). Eight additional mutations have been identified in this group, in a total of four different exons. Most of the mutations were initially identified using an assay for single-stranded conformation polymorphisms. All mutations were subsequently characterized by direct sequencing of the amplified DNA, and can be assayed by restriction enzyme digestion or allele-specific oligonucleotide hybridization.
- Published
- 1991
26. Prenatal diagnosis and linkage disequilibrium with cystic fibrosis for markers surrounding D7S8
- Author
-
Maurizio Ferrari, Silvia Russo, Dicky J. J. Halley, Michael Dean, Francis S. Collins, Giovanni Romeo, Kenneth Ward, Bruce S. Weir, Michael C. Iannuzzi, Jean A. Amos, Paula Finn, Ben A. Oostra, Jennifer R. Lynch, and Marcella Devoto
- Subjects
Genetic Markers ,0106 biological sciences ,Linkage disequilibrium ,Cystic Fibrosis ,Prenatal diagnosis ,Locus (genetics) ,Biology ,01 natural sciences ,Cystic fibrosis ,Linkage Disequilibrium ,03 medical and health sciences ,Genetic linkage ,Prenatal Diagnosis ,Genetics ,medicine ,Humans ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,medicine.disease ,Human genetics ,Pedigree ,3. Good health ,Genetic marker ,Restriction fragment length polymorphism ,DNA Probes ,Polymorphism, Restriction Fragment Length ,010606 plant biology & botany - Abstract
Three polymorphic DNA markers surrounding the D7S8 locus were tested for their usefulness in the diagnosis of cystic fibrosis (CF) by linkage analysis. The markers correspond to the loci D7S424 and D7S426. These polymorphisms were studied by centers in the U.S., the United Kingdom, the Netherlands, and Italy, using samples from populations throughout Europe and North America. The additional information provided by these probes increased the heterogeneity of the region from 50% to 58% and was essential for a completely informative diagnosis in one family. A very high degree of linkage disequilibrium was found between these markers, which span a distance of approximately 250 kb. In addition, linkage disequilibrium with CF was noted. Significant heterogeneity of linkage disequilibrium was found among the populations, both for the marker-marker pairs and between the markers and CF.
- Published
- 1990
27. A frame-shift mutation in the cystic fibrosis gene
- Author
-
Bernard Gerrard, Julie M. C. Hsu, Michael Dean, Jean A. Amos, Paula Finn, and Marga Belle White
- Subjects
Heterozygote ,Cystic Fibrosis ,Molecular Sequence Data ,Cystic Fibrosis Transmembrane Conductance Regulator ,Locus (genetics) ,Biology ,Cystic fibrosis ,Polymerase Chain Reaction ,Frameshift mutation ,Exon ,medicine ,Humans ,Insertion ,Amino Acid Sequence ,Allele ,Alleles ,Genetics ,Multidisciplinary ,Base Sequence ,Genetic disorder ,Membrane Proteins ,medicine.disease ,Molecular biology ,Cystic fibrosis transmembrane conductance regulator ,Mutation ,biology.protein ,Chromosomes, Human, Pair 7 - Abstract
Cystic fibrosis (CF) is a common recessive lethal genetic disorder, affecting 1 in 1,600 Caucasians. The disease causes defective regulation of chloride-ion transport in exocrine cells. Although in all CF families the disease is linked to a locus on chromosome 7q31, there is clinical heterogeneity in the severity of the disease and the age at which it is diagnosed. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. A three-nucleotide deletion (delta F508) causing the loss of a phenylalanine residue in the tenth exon of the CFTR gene has been found on 70% of CF chromosomes. We have now characterized a CF family in which neither parent of the affected individual carries the common mutation, and identified a two-nucleotide insertion in the CF allele of the mother. The mutation introduces a termination codon in exon 13 of the CFTR gene at residue 821, and is predicted to result in the production of a severely truncated nonfunctional protein.
- Published
- 1990
28. Erratum
- Author
-
Jean A. Amos, Anne Maddalena, Carolyn Sue Richards, Bernice A Allitto, Linda A. Bradley, Wayne W. Grody, Matthew McGinnis, Thomas W. Prior, Michael S. Watson, and Bradley W. Popovich
- Subjects
Genetics ,Cftr mutation ,business.industry ,Medicine ,business ,Genetics (clinical) - Published
- 2002
29. An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome
- Author
-
Christopher F. Hoth, Clinton T. Baldwin, Jean A. Amos, Elias O. da-Silva, and Aubrey Milunsky
- Subjects
Genetics ,Multidisciplinary ,Hearing loss ,Waardenburg syndrome ,Point mutation ,Biology ,medicine.disease ,Gene product ,Exon ,Mutation (genetic algorithm) ,medicine ,medicine.symptom ,Waardenburg Syndrome Type 1 ,Gene - Abstract
Here we report the identification and characterization of a gene defect causing Waardenburg's syndrome with hearing loss in a large Brazilian family. This demonstrates a mutation causing Waardenburg's syndrome as well as a mutation causing a form of congenital deafness. The mutation was found in the HuP2 gene, a member of the paired domain family of proteins that bind DNA and regulate gene expression. The mutation occurred in 100% of the cases with the disease in this family and was absent in a random sample of 50 unrelated control subjects. Identification of the Waardenburg's syndrome gene and future characterization of its gene product is likely to increase our understanding of the pathogenesis of this disorder and may allow prevention of deafness of this type.
- Published
- 1992
30. Clinical Findings and Linkage Studies in Familial Tuberous Sclerosis
- Author
-
A. Jewell, C. H. Yang, J Haines, Herman E. Wyandt, M. P. Short, E. Andermann, B. Bejjani, David J. Kwiatkowski, Jean A. Amos, and H. MacFarlane
- Subjects
Genetics ,Genetic Linkage ,General Neuroscience ,Calcium-Binding Proteins ,Microfilament Proteins ,Microfilament Protein ,Biology ,medicine.disease ,Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,Pedigree ,law.invention ,Tuberous sclerosis ,History and Philosophy of Science ,Tuberous Sclerosis ,law ,Genetic linkage ,Calcium-binding protein ,medicine ,Humans ,Gelsolin ,Polymerase chain reaction - Published
- 1991
31. Congenital Bilateral Absence of the Vas Deferens
- Author
-
Aubrey Milunsky, Michael Dean, Thomas A. Maher, Robert D. Oates, Bernard Gerrard, Marga Belle White, Arturo Anguiano, Jean A. Amos, and Claudia Stewart
- Subjects
Infertility ,Gynecology ,Pathology ,medicine.medical_specialty ,business.industry ,Vas deferens ,General Medicine ,Gene mutation ,medicine.disease ,Congenital absence of the vas deferens ,Cystic fibrosis ,Male infertility ,medicine.anatomical_structure ,Agenesis ,medicine ,Sex organ ,business - Abstract
Objective. —Almost all males with cystic fibrosis (CF) have absent vasa deferentia. It has been suggested that otherwise healthy males with congenital bilateral absence of the vas deferens (CBAVD), previously considered a distinct genetic entity, have an increased frequency of CF gene mutations. This study examined the genetic commonality of these two disorders. Design. —We typed six common CF gene mutations in 25 patients with CBAVD. Additional rare mutations were sought using single-stranded conformation polymorphisms and direct DNA sequencing. When rare mutations were found, they were sought in a large sample of both CF patients and obligate CF carriers to exclude them as polymorphisms. Setting. —All the patients presented to a male infertility clinic of a teaching hospital. Subjects. —Twenty-five unselected, unrelated azoospermic men with CBAVD, most of them of Northern European ancestry. Results. —Sixteen (64%) of the 25 men with CBAVD had at least one detectable CF mutation, 16 times the expected frequency (P Conclusions. —Some, if not all, otherwise healthy men with CBAVD reflect a newly recognized, primarily genital, phenotype of CF. Prior to sperm aspiration to remedy infertility, CF mutation analysis should be recommended for them and their partners, as well as for their relatives. (JAMA. 1992;267:1794-1797)
- Published
- 1992
32. Three additional DNA polymorphisms in the met gene and D7S8 locus: Use in prenatal diagnosis of cystic fibrosis
- Author
-
Ray White, Jean A. Amos, George F. Vande Woude, Peter O'Connell, Morag Park, Michael Dean, Mark Leppert, and Deborah G. Phillips
- Subjects
Genetic Markers ,Cystic Fibrosis ,TaqI ,Locus (genetics) ,Pedigree chart ,Prenatal diagnosis ,Cystic fibrosis ,DNA sequencing ,chemistry.chemical_compound ,Prenatal Diagnosis ,medicine ,Humans ,Gene ,Alleles ,Genetics ,business.industry ,Genetic Carrier Screening ,Chromosome Mapping ,DNA ,medicine.disease ,Pedigree ,chemistry ,Pediatrics, Perinatology and Child Health ,Restriction fragment length polymorphism ,business ,Chromosomes, Human, Pair 7 ,Polymorphism, Restriction Fragment Length - Abstract
We have used cloned DNA sequences from the 5′ end of the met locus and the D7S8 locus to locate new restriction fragment length polymorphisms. TaqI and MspI polymorphisms with frequencies of 0.34/0.66 and 0.10/0.90, respectively, for met and a PvuII polymorphism (0.15/0.85) at D7S8 are described. We used these new markers to analyze our reference panel of cystic fibrosis pedigrees and found that they provided additional information in several families. No evidence for recombination was observed between the 5′ end of met and previously described met markers. We present examples of the use of the met markers in the clinical diagnosis of cystic fibrosis and summarize our analysis of 29 clinical cases including eight prenatal diagnoses. We conclude that DNA-based prediction of cystic fibrosis is an effective clinical diagnostic procedure.
- Published
- 1987
33. Absence of duplication of chromosome 21 genes in familial and sporadic Alzheimer's disease
- Author
-
James W. Bodfish, Linda Nee, James F. Gusella, Peter St George-Hyslop, Daniel A. Pollen, Ronald J. Polinsky, Robert G. Feldman, David A. Drachman, Marcel Kinsbourne, Luigi Amaducci, Jean A. Amos, Jean-François Foncin, L. Adrienne Cupples, Rudolph E. Tanzi, Curtis K. Deutsch, Amalia C. Bruni, Dianne O'Sullivan, Rachael L. Neve, Paul C. Watkins, Richard H. Myers, and John H. Growdon
- Subjects
Genetics ,Down syndrome ,Amyloid ,Multidisciplinary ,Autosome ,Amyloid beta ,Chromosomes, Human, Pair 21 ,Genetic Linkage ,Biology ,medicine.disease ,Genes ,Genetic marker ,Alzheimer Disease ,Gene duplication ,medicine ,biology.protein ,Humans ,Alzheimer's disease ,Chromosome 21 ,Gene ,Alleles ,Polymorphism, Restriction Fragment Length - Abstract
The possibility that Alzheimer's disease (AD) is caused by overexpression or duplication of one or more genes on chromosome 21 has been raised by the observation of AD-like neuropathologic changes in individuals with Down syndrome and by the mapping of both the defect for familial AD and the amyloid beta protein gene to this autosome. Possible duplication on chromosome 21 was investigated in both familial and sporadic AD by means of restriction fragment length polymorphisms for the amyloid and SODI loci, as well as for DNA markers in the vicinity of the familial AD defect and in the critical Down syndrome region of chromosome 21. No evidence of increased DNA dosage was observed in either brain or leukocytes of patients with inherited or sporadic forms of AD. Duplication of these regions is therefore not a frequent event in either form of AD. Furthermore, no significant allelic association was detected between AD and any of the loci, including the amyloid and SODI genes, providing no support for the hypothesis that defects in these specific genes are the primary cause of AD.
- Published
- 1987
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