Open Access. Powered by Scholars. Published by Universities.®

Life Sciences Commons™

Open Access. Powered by Scholars. Published by Universities.®

Genetics and Genomics

Selected Works

2012

Articles 31 - 60 of 110

Full-Text Articles in Life Sciences

Disparities In Allele Frequencies And Population Differentiation For 101 Disease-Associated Single Nucleotide Polymorphisms Between Puerto Ricans And Non-Hispanic Whites, Josiemer Mattei, Laurence D. Parnell, Chao-Qiang Lai, Bibiana Garcia-Bailo, Xian Adiconis, Jian Shen, Donna Arnett, Serkalem Demissie, Katherine L. Tucker, Jose M. Ordovas Aug 2012

Disparities In Allele Frequencies And Population Differentiation For 101 Disease-Associated Single Nucleotide Polymorphisms Between Puerto Ricans And Non-Hispanic Whites, Josiemer Mattei, Laurence D. Parnell, Chao-Qiang Lai, Bibiana Garcia-Bailo, Xian Adiconis, Jian Shen, Donna Arnett, Serkalem Demissie, Katherine L. Tucker, Jose M. Ordovas

Katherine L. Tucker

Background: Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection pressures. Such genetic information is limited in Puerto Ricans, the second largest Hispanic ethnic group in the US, and a group with high prevalence of chronic disease. We determined allele frequencies and population differentiation for 101 single nucleotide polymorphisms (SNPs) in 30 genes involved in major metabolic and disease-relevant pathways in Puerto Ricans (n = 969, ages 45–75 years) and compared them to …

Go to article

Gene Transfer In The Lung Using Recombinant Adeno-Associated Virus, Alisha Gruntman, Christian Mueller, Terence Flotte, Guangping Gao Aug 2012

Gene Transfer In The Lung Using Recombinant Adeno-Associated Virus, Alisha Gruntman, Christian Mueller, Terence Flotte, Guangping Gao

Christian Mueller

Adeno-associated virus (AAV) is a small replication-deficient DNA virus belonging to the Parvovirinae family. It has a single-stranded ∼4.7-kb genome. Recombinant AAV (rAAV) is created by replacing the viral rep and cap genes with the transgene of interest along with promoter and polyadenylation sequences. The short viral inverted terminal repeats must remain intact for replication and packaging in production, as well as vector genome processing and persistence in the transduction process. The AAV capsid (serotype) determines the tissue tropism of the rAAV vector. In this unit we will discuss serotype selection for lung targeting along with the factors effecting efficient …

Go to article

Accumulation Of Extracellular Carbohydrates In A Scytonemin-Deficient Mutant Of Nostoc Punctiforme Exposed To Uva Stress, Tanya Soule Jul 2012

Accumulation Of Extracellular Carbohydrates In A Scytonemin-Deficient Mutant Of Nostoc Punctiforme Exposed To Uva Stress, Tanya Soule

Tanya Soule

No abstract provided.

Go to article

Serum Microrna-122 And Mir-155 As Biomarkers Of Liver Injury And Inflammation In Models Of Acute And Chronic Liver Disease, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Jeanine Ward, Ivan Levin, Hawau Alao, Karen Kodys, Gyongyi Szabo Jul 2012

Serum Microrna-122 And Mir-155 As Biomarkers Of Liver Injury And Inflammation In Models Of Acute And Chronic Liver Disease, Shashi Bala, Jan Petrasek, Shiv Mundkur, Donna Catalano, Jeanine Ward, Ivan Levin, Hawau Alao, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Background: MicroRNAs (miRs) are small non-coding molecules that regulate gene expression. MiRs expression levels change not only in diseased tissues but also in circulation. Further, miRs are stable in frozen samples that make them attractive for biomarker discovery. Recent reports suggest altered expression of circulating miRNAs in various diseases. MiR-122 is highly abundant in hepatocytes where it regulates different metabolic pathways while miR-155 is a central regulator of inflammation. The aim of this study was to evaluate circulating miRNAs as potential markers of hepatocyte damage and inflammation in liver diseases. Methods: Serum/plasma and liver samples were collected from C57/BL6 mice …

Go to article

Protamine-Like Proteins In 12 Sequenced Species Of Drosophila, Zain Alvi, Tin-Chun Chu, Valerie Schawaroch, Angela Klaus Jul 2012

Protamine-Like Proteins In 12 Sequenced Species Of Drosophila, Zain Alvi, Tin-Chun Chu, Valerie Schawaroch, Angela Klaus

Tin-Chun Chu, Ph.D.

No abstract provided.

Go to article

Identification And Bioinformatic Analyses Of Vanillate Operon In Cyanobacterium Synechococcus Sp. Iu 625, Robert Newby, Tin-Chun Chu Jun 2012

Identification And Bioinformatic Analyses Of Vanillate Operon In Cyanobacterium Synechococcus Sp. Iu 625, Robert Newby, Tin-Chun Chu

Tin-Chun Chu, Ph.D.

No abstract provided.

Go to article

Bioinformatic Analysis Of Cyanobacterial Mercuric Resistance Genes And Identification Of Synechococcus Sp. Iu 625 Putative Mercuric Resistance Genes, Lee Lee, Chiedozie Okafor, Matthew Rienzo, Tin-Chun Chu Jun 2012

Bioinformatic Analysis Of Cyanobacterial Mercuric Resistance Genes And Identification Of Synechococcus Sp. Iu 625 Putative Mercuric Resistance Genes, Lee Lee, Chiedozie Okafor, Matthew Rienzo, Tin-Chun Chu

Tin-Chun Chu, Ph.D.

No abstract provided.

Go to article

"Genetics In Geographically Structured Populations: Defining, Estimating And Interpreting Fst.", Kent E. Holsinger, Bruce S. Weir Jun 2012

"Genetics In Geographically Structured Populations: Defining, Estimating And Interpreting Fst.", Kent E. Holsinger, Bruce S. Weir

Kent E Holsinger

Wright's F-statistics, and especially F(ST), provide important insights into the evolutionary processes that influence the structure of genetic variation within and among populations, and they are among the most widely used descriptive statistics in population and evolutionary genetics. Estimates of F(ST) can identify regions of the genome that have been the target of selection, and comparisons of F(ST) from different parts of the genome can provide insights into the demographic history of populations. For these reasons and others, F(ST) has a central role in population and evolutionary genetics and has wide applications in fields that range from disease association mapping …

Go to article

Codon Optimization For Alpha 1-Antitrypsin Disease, Timothy Menz, Qiushi Tang, Lina Song, Christian Mueller, Terence R. Flotte May 2012

Codon Optimization For Alpha 1-Antitrypsin Disease, Timothy Menz, Qiushi Tang, Lina Song, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha 1-antitrypsin deficiency is a genetic disorder caused by defective production of alpha 1-antitrypsin (AAT). Gene therapy approaches have been conducted in patients with AAT deficiency with successful AAT expression, but not to the therapeutic levels required to reduce the risk of emphysema. Codon optimization, a somewhat new and evolving technique, is used by many scientists to maximize protein expression in living organisms by altering translational and transcriptional efficiency as well as protein refolding. The purpose of this study was to develop single stranded and double stranded AAT gene constructs, test their protein expression in vitro, and compare with those …

Go to article

A Unified View Of Base Excision Repair, Karen Almeida, Robert Sobol Apr 2012

A Unified View Of Base Excision Repair, Karen Almeida, Robert Sobol

Karen H Almeida

Base excision repair (BER) proteins act upon a significantly broad spectrum of DNA lesions that result from endogenous and exogenous sources. Multiple sub-pathways of BER (short-path or longpatch) and newly designated DNA repair pathways (e.g., SSBR and NIR) that utilize BER proteins complicate any comprehensive understanding of BER and its role in genome maintenance, chemotherapeutic response, neurodegeneration, cancer or aging. Herein, we propose a unified model of BER, comprised of three functional processes: Lesion Recognition/Strand Scission, Gap Tailoring and DNA Synthesis/Ligation, each represented by one or more multiprotein complexes and coordinated via the XRCC1/DNA Ligase III and PARP1 scaffold proteins. …

Go to article

Identification Of Sonic Hedgehog As A Candidate Gene Responsible For Holoprosencephaly, Helen Donis-Keller, E Belloni, M Muenke, E Roessler, G Traverse, J Siegel-Bartelt, A Frumkin, H Mitchell, C Helms, A Hing, H Heng, B Kroop, D Martindale, J Rommens, L Tsui, S Scherer Apr 2012

Identification Of Sonic Hedgehog As A Candidate Gene Responsible For Holoprosencephaly, Helen Donis-Keller, E Belloni, M Muenke, E Roessler, G Traverse, J Siegel-Bartelt, A Frumkin, H Mitchell, C Helms, A Hing, H Heng, B Kroop, D Martindale, J Rommens, L Tsui, S Scherer

Helen Donis-Keller

Holoprosencephaly (HPE) is a genetically and phenotypically heterogenous disorder involving the development of forebrain and midface, with an incidence of 1:16,000 live born and 1:250 induced abortions. This disorder is associated with several distinct facies and phenotypic variability: in the most extreme cases, anophthalmia or cyclopia is evident along with a congenital absence of the mature nose. The less severe form features facial dysmorphia characterized by ocular hypertelorism, defects of the upper lip and/or nose, and absence of the olfactory nerves or corpus callosum. Several intermediate phenotypes involving both the brain and face have been described. One of the gene …

Go to article

7q11.23 Deletions In Williams Syndrome Arise As A Consequence Of Unequal Meiotic Crossover, Helen Donis-Keller, Zsolt Urbán, C Helms, G Fekete, Katalin Csiszár, D Bonnet, A Munnich, C Boyd Apr 2012

7q11.23 Deletions In Williams Syndrome Arise As A Consequence Of Unequal Meiotic Crossover, Helen Donis-Keller, Zsolt Urbán, C Helms, G Fekete, Katalin Csiszár, D Bonnet, A Munnich, C Boyd

Helen Donis-Keller

Williams syndrome (WS) (Williams et al. 1961; Beurenet al. 1962) is a multisystem disorder characterized by mental retardation, a specific neurobehavioral profile,characteristic facies, infantile hypercalcemia, cardiovascular abnormalities, progressive joint limitation, hernias, and soft skin. Recent studies have shown that hemizygosity at the elastin (ELN) gene locus on chromosome7q is associated with WS (Ewart et al. 1993). Furthermore, two FISH studies using cosmid recombinants containing the 5' or the 3' end of the ELN gene revealed deletion of the entire ELN gene in 90%-96% of classical WS cases (Lowery et al. 1995; Nickerson et al. 1995). However, the size of the …

Go to article

Comparative Genomic Hybridization Of Human Malignant Gliomas Reveals Multiple Amplification Sites And Nonrandom Chromosomal Gains And Losses, Helen Donis-Keller, Evelin Schròck, Gundula Thiel, Tanka Lozanova, Stanislas Du Manoir, Marie-Christine Meffert, Anna Jauch, Michael Speicher, Peter Nürnberg, Siegfried Vogel, Werner Janisch, Thomas Ried, Regine Witkowski, Thomas Cremer Apr 2012

Comparative Genomic Hybridization Of Human Malignant Gliomas Reveals Multiple Amplification Sites And Nonrandom Chromosomal Gains And Losses, Helen Donis-Keller, Evelin Schròck, Gundula Thiel, Tanka Lozanova, Stanislas Du Manoir, Marie-Christine Meffert, Anna Jauch, Michael Speicher, Peter Nürnberg, Siegfried Vogel, Werner Janisch, Thomas Ried, Regine Witkowski, Thomas Cremer

Helen Donis-Keller

Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five …

Go to article

Recombinant Mapping Of The Familial Hyperinsulinism Gene To An 0.8 Cm Region On Chromosome 11p15.1 And Demonstration Of A Founder Effect In Ashkenazi Jews, Helen Donis-Keller, Benjamin Glaser, Ken Chiu, Li Liu, Roberto Anker, Ann Nestorowicz, Nancy Cox, Heddy Landau, Kalser Nurit, Paul Thornton, Charles Stanley, Erol Cerasl, Lester Baker, M. Alan Permutt Apr 2012

Recombinant Mapping Of The Familial Hyperinsulinism Gene To An 0.8 Cm Region On Chromosome 11p15.1 And Demonstration Of A Founder Effect In Ashkenazi Jews, Helen Donis-Keller, Benjamin Glaser, Ken Chiu, Li Liu, Roberto Anker, Ann Nestorowicz, Nancy Cox, Heddy Landau, Kalser Nurit, Paul Thornton, Charles Stanley, Erol Cerasl, Lester Baker, M. Alan Permutt

Helen Donis-Keller

A gene for autosomal recessive familial hyperinsulinism (HI) (OMIM: 256450), a neonatal metabolic disease characterized by inappropriate insulin secretion in the presence of severe hypoglycemia, was recently mapped to a 6.6 cM interval between the markers D11S926 and D11S928 onchromosome 11p in 15 families (1). In the current study we evaluated six additional families and five new markers, and further localized the gene between D11S419 and D11S1310. Using genotype data from CEPH Version 7 and data generated from this study, this region was estimated to be 0.8 cM in length. Significant linkage disequilibrium between markers and the HIgene was observed …

Go to article

Sequence-Ready Contig For The 1.4-Cm Ductal Carcinoma In Situ Loss Of Heterozygosity Region On Chromosome 8p22–P23, Helen Donis-Keller, Jen Wang, Diane Radford, Matthew Holt, C Helms, A Goate, W Brandt, M Parik, Nancy Phillips, K Deschryver, M Schuh, Keri Fair, Jon Ritter, P Marshall Apr 2012

Sequence-Ready Contig For The 1.4-Cm Ductal Carcinoma In Situ Loss Of Heterozygosity Region On Chromosome 8p22–P23, Helen Donis-Keller, Jen Wang, Diane Radford, Matthew Holt, C Helms, A Goate, W Brandt, M Parik, Nancy Phillips, K Deschryver, M Schuh, Keri Fair, Jon Ritter, P Marshall

Helen Donis-Keller

We report the construction of an ∼1.7-Mb sequence-ready YAC/BAC clone contig of 8p22–p23. This chromosomal region has been associated with frequent loss of heterozygosity (LOH) in breast, ovarian, prostate, head and neck, and liver cancer. We first constructed a meiotic linkage map for 8p to resolve previously reported conflicting map orders from the literature. The target region containing a putative tumor suppressor gene was defined by allelotyping 65 cases of sporadic ductal carcinoma in situ with 18 polymorphic markers from 8p. The minimal region of loss encompassed the interval between D8S520 and D8S261, and one tumor had loss of D8S550 …

Go to article

Isolation, Characterization, And Chromosomal Mapping Of The Human Nkx6.1 Gene (Nkx6a), A New Pancreatic Islet Homeobox Gene, Helen Donis-Keller, Hiroshi Inoue, Abraham Rudnick, Michael German, Rosalie Veile, M. Alan Permutt Apr 2012

Isolation, Characterization, And Chromosomal Mapping Of The Human Nkx6.1 Gene (Nkx6a), A New Pancreatic Islet Homeobox Gene, Helen Donis-Keller, Hiroshi Inoue, Abraham Rudnick, Michael German, Rosalie Veile, M. Alan Permutt

Helen Donis-Keller

Nkx6.1 (gene symbol NKX6A), a new member of the NK homeobox gene family, was recently identified in rodent pancreatic islet β-cell lines. The pattern of expression suggested that this gene product might be important for control of islet development and/or regulation of insulin biosynthesis. We now report cloning of human NKX6A, characterization of its genomic structure, and its chromosomal localization. The predicted protein of human NKX6A contained 367 amino acids and had 97% identity to the hamster protein. The highly conserved NK decapeptide and homeodomain regions were identical between human and hamster, suggesting functional importance of these domains. The coding …

Go to article

Identification Of A Human Lmx1 (Lmx1.1)-Related Gene, Lmx1.2: Tissue-Specific Expression And Linkage Mapping On Chromosome 9, Helen Donis-Keller, Christopher Iannotti, Hiroshi Inoue, Ernesto Bernal-Mizrachi, Minoru Aoki, Li Liu, Michael German, M. Alan Permutt Apr 2012

Identification Of A Human Lmx1 (Lmx1.1)-Related Gene, Lmx1.2: Tissue-Specific Expression And Linkage Mapping On Chromosome 9, Helen Donis-Keller, Christopher Iannotti, Hiroshi Inoue, Ernesto Bernal-Mizrachi, Minoru Aoki, Li Liu, Michael German, M. Alan Permutt

Helen Donis-Keller

LMX1 is a LIM-homeodomain (LIM-HD)-containing protein expressed selectively in insulin-producing β-cell lines, and it it has been shown to activate insulin gene transcription. The human LMX1 gene was mapped by fluorescencein situhybridization to chromosome region 1q22–q23, yet Churchet al.(1994,Nat. Genet.6: 98–105) identified two exon-trapping products from human chromosome 9 that were highly homologous to hamster LMX1. In the current study, we demonstrate tissue-specific expression of an LMX1 (now known as LMX1.1)-related gene, named LMX1.2. The chicken C-LMX1 gene, recently cloned using the hamster LMX1.1 sequence and shown to specify dorsal cell fate during vertebrate …

Go to article

Supravalvular Aortic Stenosis: A Splice Site Mutation Within The Elastin Gene Results In Reduced Expression Of Two Aberrantly Spliced Transcripts, Helen Donis-Keller, Zsolt Urbán, Virginia Michels, Stephen Thibodeau, Katalin Csiszár, C Boyd Apr 2012

Supravalvular Aortic Stenosis: A Splice Site Mutation Within The Elastin Gene Results In Reduced Expression Of Two Aberrantly Spliced Transcripts, Helen Donis-Keller, Zsolt Urbán, Virginia Michels, Stephen Thibodeau, Katalin Csiszár, C Boyd

Helen Donis-Keller

We have screened the elastin gene for mutations responsible for supravalvular aortic stenosis (SVAS) in two large, independently collected families with isolated (nonsyndromic) SVAS. By single-strand conformation polymorphism and heteroduplex analysis, we have identified a C to G transversion within the acceptor splice site of exon 16 in SVAS patients from both families. This mutation segregates in both families with high penetrance of SVAS, and all affected individuals carry the mutation. Haplotype analysis by using closely linked polymorphisms, including a previously unreported BfaI restriction fragment length polymorphism within the 3’-UTR of the elastin gene, indicates that the mutations found …

Go to article

High Levels Of Loss At The 17p Telomere Suggest The Close Proximity Of A Tumour Suppressor, Helen Donis-Keller, G White, M Stack, M Santibáñez-Koref, D Liscia, T Venesio, Jen Wang, C Helms, D Betticher, H Altermatt, P Hoban, J Heighway Apr 2012

High Levels Of Loss At The 17p Telomere Suggest The Close Proximity Of A Tumour Suppressor, Helen Donis-Keller, G White, M Stack, M Santibáñez-Koref, D Liscia, T Venesio, Jen Wang, C Helms, D Betticher, H Altermatt, P Hoban, J Heighway

Helen Donis-Keller

High levels of loss of distal markers on 17p13.3 in breast cancer suggested the presence within the region of at least one tumour-suppressor gene. Here we describe the derivation of two biallelic polymorphisms from the 17p telomeric yeast artificial chromosome (YAC) TYAC98. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR analysis demonstrated that the high level of allelic imbalance observed in breast tumours represented loss of constitutional heterozygosity (LOH) and that this LOH extended to the telomere. Lung carcinoma (but not Wilms' tumour)-derived DNA again revealed a high level of loss of subtelomeric 17p sequences. Telomeric microsatellite polymorphisms …

Go to article

Genetic Fine Mapping Of The Gene For Nonsyndromic Congenital Retinal Nonattachment., Helen Donis-Keller, N Ghiasvand, T Fleming, C Helms, Aledavood Avisa Apr 2012

Genetic Fine Mapping Of The Gene For Nonsyndromic Congenital Retinal Nonattachment., Helen Donis-Keller, N Ghiasvand, T Fleming, C Helms, Aledavood Avisa

Helen Donis-Keller

Autosomal recessive nonsyndromic congenital retinal nonattachment (NCRNA) comprises congenital insensitivity to light, massive retrolental mass, shallow anterior chamber, microphthalmia, and nystagmus in otherwise normal individuals. Polymerase chain reaction-based linkage analyses of polymorphic microsatellite markers in the 10q21 region on DNA samples from 106 individuals provide evidence that the NCRNA locus is within an interval of ∼0.6–1.5 cM, flanked by the markers D10S522 and D10S1418. Haplotype analysis demonstrated a unique founder haplotype shared by 100% of the NCRNA chromosomes. These results indicate a founder effect and the strong possibility of a single mutation as the cause of the disease in the …

Go to article

Mapping Human Telomere Regions With Yac And P1 Clones: Chromosome-Specific Markers For 27 Telomeres Including 149 Stss And 24 Polymorphisms For 14 Proterminal Regions, Helen Donis-Keller, A Vocero-Akbani, C Helms, Jen Wang, F Sanjurjo, J Korte-Sarfaty, Rosalie Veile, L Liu, A Jauch, A Burgess, A Hing, Matthew Holt, S Ramachandra, A Whelan, R Anker, L Ahrent, M Chen, M Gavin, K Iannantuoni, S Morton, Sunil Pandit, C Read, Todd Steinbrueck, Christopher Warlick, D Smoller Apr 2012

Mapping Human Telomere Regions With Yac And P1 Clones: Chromosome-Specific Markers For 27 Telomeres Including 149 Stss And 24 Polymorphisms For 14 Proterminal Regions, Helen Donis-Keller, A Vocero-Akbani, C Helms, Jen Wang, F Sanjurjo, J Korte-Sarfaty, Rosalie Veile, L Liu, A Jauch, A Burgess, A Hing, Matthew Holt, S Ramachandra, A Whelan, R Anker, L Ahrent, M Chen, M Gavin, K Iannantuoni, S Morton, Sunil Pandit, C Read, Todd Steinbrueck, Christopher Warlick, D Smoller

Helen Donis-Keller

A YAC library enriched for telomere clones was constructed and screened for the humantelomere-specific repeat sequence (TTAGGG). Altogether 196 TYAC library clones were studied: 189 new TYAC clones were isolated, 149 STSs were developed for 132 different TY-ACs, and 39P1 clones were identified using 19 STSs from 16 of the TYACs. A combination of mappingmethods including fluorescence in situ hybridization, somatic cell hybrid panels, clamped homogeneous electric fields, meiotic linkage, and BLASTN sequence analysis was utilized to characterize the resource. Forty-five of the TYACs map to 31 specific telomere regions. Twenty-four linkage markers were developed and mapped within 14 proterminal …

Go to article

Subregional Localization Of 21 Chromosome 7-Specific Expressed Sequence Tags (Ests) By Fish Using Newly Identified Yacs And P1s, Helen Donis-Keller, S Morton, Rosalie Veile, Cynthia Helms, Martin Lee, Wen-Lin Kuo, Joe Gray Apr 2012

Subregional Localization Of 21 Chromosome 7-Specific Expressed Sequence Tags (Ests) By Fish Using Newly Identified Yacs And P1s, Helen Donis-Keller, S Morton, Rosalie Veile, Cynthia Helms, Martin Lee, Wen-Lin Kuo, Joe Gray

Helen Donis-Keller

Twenty-one putative chromosome 7-derived expressed sequence tags (ESTs) identified 33 yeast artificial chromosomes (YACs) or P1 clones, which were then used as reagents for physical mapping. FISH mapping established that the ESTs contained within these clones were distributed throughout chromosome 7, with all major cytogenetic bands represented, except 7p13–p15, 7p11, 7q31.2, and 7q35. Each EST sequence identified at least one other sequence in publicly available databases (using search tools such as BLASTN, basic local alignment search tool), and many of the ESTs identified cDNAs and several genomic DNA sequences. However, 7 ESTs did not identify highly significant matches (P< 1 …

Go to article

The Finding Of A Somatic Deletion In Ret Exon 15 Clarified The Sporadic Nature Of A Medullary Thyroid Carcinoma Suspected To Be Familial, Helen Donis-Keller, J Oriola, I Halperin, F Rivera-Fillat Apr 2012

The Finding Of A Somatic Deletion In Ret Exon 15 Clarified The Sporadic Nature Of A Medullary Thyroid Carcinoma Suspected To Be Familial, Helen Donis-Keller, J Oriola, I Halperin, F Rivera-Fillat

Helen Donis-Keller

Medullary thyroid carcinoma (MTC) occurs both sporadically and in the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between both is important for future clinical management. We report a family initially described as a familial MTC by pentagastrin stimulation test and clinical outcome, in which we found a 12 bp deletion within the catalytic domain of the protooncogene RET in the index case tumor alone. Linkage study suggests that it is a sporadic MTC. Therefore, in view of these results, in kindred with just one MTC case, borderline pentagastrin test values must be carefully assessed. In …

Go to article

The Multiple Endocrine Neoplasia Type 2b Point Mutation Alters Long-Term Regulation And Enhances The Transforming Capacity Of The Epidermal Growth Factor Receptor, Helen Donis-Keller, Sunil Pandit, Takeo Iwamoto, John Tomich, Linda Pike Apr 2012

The Multiple Endocrine Neoplasia Type 2b Point Mutation Alters Long-Term Regulation And Enhances The Transforming Capacity Of The Epidermal Growth Factor Receptor, Helen Donis-Keller, Sunil Pandit, Takeo Iwamoto, John Tomich, Linda Pike

Helen Donis-Keller

The RET proto-oncogene encodes a member of the receptor tyrosine kinase family. Multiple endocrine neoplasia type 2B (MEN 2B) is caused by the mutation of a conserved methionine to a threonine in the catalytic domain of the RET kinase. When the MEN 2B point mutation was introduced into the epidermal growth factor (EGF) receptor (M857T EGFR), the intrinsic tyrosine kinase activity of the mutant receptor was similar to that of wild-type EGF receptor and remained ligand-dependent. However, the mutant receptor showed an enhanced transforming capacitycompared to the wild-type receptor as judged by its ability to mediate the growth of NIH …

Go to article

Index, Comprehensive Microsatellite, And Unified Linkage Maps Of Human Chromosome 14 With Cytogenetic Tie Points And A Telomere Microsatellite Marker, Helen Donis-Keller, Sunil Pandit, Jen Wang, Rosalie Veile, Santosh Mishra, Christopher Warlick Apr 2012

Index, Comprehensive Microsatellite, And Unified Linkage Maps Of Human Chromosome 14 With Cytogenetic Tie Points And A Telomere Microsatellite Marker, Helen Donis-Keller, Sunil Pandit, Jen Wang, Rosalie Veile, Santosh Mishra, Christopher Warlick

Helen Donis-Keller

Three sets of linkage maps (index, comprehensive microsatellite, and unified) have been constructed for human chromosome 14 based on genotypes from the CEPH reference pedigrees. The index maps consist of 18 microsatellite markers, with heterozygosities of at least 68% and intermarker spacing no greater than 11 cM. The sex-average comprehensive microsatellite map is 125 cM in length and includes 115 markers with 54 loci uniquely placed with odds for marker order of at least 1000:1. The sex-average index map length is 121 cM, and the female- and male-specificmaps are 143 and 101 cM, respectively. A unified map was also constructed …

Go to article

The Ceph Consortium Linkage Map Of Human Chromosome 11, M Litt, P Kramer, E. Kort, P Fain, S Cox, D Root, R White, J Weissenbach, Helen Donis-Keller, R Gatti, J Weber, Y Nakamura, C Julier, K Hayashi, N Spurr, M Dean, J Mandel, K Kidd, T Kruse, A Retief, A Bale, T Meo, G Vergnaud, S Warren, H Willard Apr 2012

The Ceph Consortium Linkage Map Of Human Chromosome 11, M Litt, P Kramer, E. Kort, P Fain, S Cox, D Root, R White, J Weissenbach, Helen Donis-Keller, R Gatti, J Weber, Y Nakamura, C Julier, K Hayashi, N Spurr, M Dean, J Mandel, K Kidd, T Kruse, A Retief, A Bale, T Meo, G Vergnaud, S Warren, H Willard

Helen Donis-Keller

The CEPH consortium framework map of chromosome 11 is presented. The map was generated from CEPH family DNAs with 181 probe/enzyme combinations contributed by 20 laboratories. Seventy-seven of the loci are defined by microsatellite polymorphisms that can be typed by the PCR. A total of 42 loci have been placed on the map with likelihood support of at least 1000:1. The female, male, and sex-average maps extend for 179.6, 110.8, and 145.3 cM, respectively. The largest interval on the sex-average map is less than 11 cM, and the average distance between uniquely placed loci is 4 cM. The genotypic data …

Go to article

A Gene Encoding A Transmembrane Protein Is Mutated In Patients With Diabetes Mellitus And Optic Atrophy (Wolfram Syndrome), Helen Donis-Keller, Hiroshi Inoue, Yukio Tanizawa, Jon Wasson, Philip Behn, Kamini Kalidas, Ernesto Bernal-Mizrachi, Mike Mueckler, Helen Marshall, Patricia Crock, Douglas Rogers, Masahiko Mikuni, Hisashi Kumashiro, Koichiro Higashi, Gen Sobue, Yoshitomo Oka, M. Permutt Apr 2012

A Gene Encoding A Transmembrane Protein Is Mutated In Patients With Diabetes Mellitus And Optic Atrophy (Wolfram Syndrome), Helen Donis-Keller, Hiroshi Inoue, Yukio Tanizawa, Jon Wasson, Philip Behn, Kamini Kalidas, Ernesto Bernal-Mizrachi, Mike Mueckler, Helen Marshall, Patricia Crock, Douglas Rogers, Masahiko Mikuni, Hisashi Kumashiro, Koichiro Higashi, Gen Sobue, Yoshitomo Oka, M. Permutt

Helen Donis-Keller

Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1appears to function in survival of islet -cells and neurons.

Go to article

Nonsyndromic Congenital Retinal Nonattachment Gene Maps To Human Chromosome Band 10q21, Helen Donis-Keller, N Ghiasvand, A Kanis, C Helms, V Sheffield, E Stone Apr 2012

Nonsyndromic Congenital Retinal Nonattachment Gene Maps To Human Chromosome Band 10q21, Helen Donis-Keller, N Ghiasvand, A Kanis, C Helms, V Sheffield, E Stone

Helen Donis-Keller

Nonsyndromic congenital retinal nonattachment (NCRNA) comprises congenital insensitivity to light, massive retrolental mass, shallow anterior chamber, microphthalmia, and nystagmus. We searched for the location of the gene responsible for an autosomal recessive form of NCRNA by using DNA samples from 36 individuals from a founding population. To this end we applied homozygosity mapping and a DNA pooling strategy using genomewide screen polymorphic microsatellite markers. We used two DNA pools, one pool contained DNA from 16 individuals affected with NCRNA. The second pool contained DNA from 20 normal carrier individuals, the parents of the patients. The polymorphic microsatellite markers were polymerase …

Go to article

Regression Approaches For Microarray Data Analysis, Mark R. Segal, Kam D. Dahlquist, Bruce R. Conklin Apr 2012

Regression Approaches For Microarray Data Analysis, Mark R. Segal, Kam D. Dahlquist, Bruce R. Conklin

Mark R Segal

A variety of new procedures have been devised to handle the two sample comparison (e.g., tumor versus normal tissue) of gene expression values as measured with microarrays. Such new methods are required in part because of some defining characteristics of microarray-based studies: (i) the very large number of genes contributing expression measures which far exceeds the number of samples (observations) available, and (ii) the fact that by virtue of pathway/network relationships, the gene expression measures tend to be highly correlated. These concerns are exacerbated in the regression setting, where the objective is to relate gene expression, simultaneously for multiple genes, …

Go to article

A Novel Topology For Representing Protein Folds, Mark R. Segal Apr 2012

A Novel Topology For Representing Protein Folds, Mark R. Segal

Mark R Segal

Various topologies for representing three dimensional protein structures have been advanced for purposes ranging from prediction of folding rates to ab initio structure prediction. Examples include relative contact order, Delaunay tessellations, and backbone torsion angle distributions. Here we introduce a new topology based on a novel means for operationalizing three dimensional proximities with respect to the underlying chain. The measure involves first interpreting a rank-based representation of the nearest neighbors of each residue as a permutation, then determining how perturbed this permutation is relative to an unfolded chain. We show that the resultant topology provides improved association with folding and …

Go to article

First Prev Next Last