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R Agarwala

Publications and source records attributed to R Agarwala.

At least 19 recordsLinked to original sources
PubMed2000

A fast and scalable radiation hybrid map construction and integration strategy.

This paper describes a fast and scalable strategy for constructing a radiation hybrid (RH) map from data on different RH panels. The maps on each panel are then integrated to produce a single RH map for the genome. Recurring problems in using maps from several sources are that the maps use different markers, the maps do not place the overlapping markers in same order, and the objective functions for map quality are incomparable. We use methods from combinatorial optimization to develop a strategy that addresses these issues. We show that by the standard objective functions of obligate chromosome breaks and maximum likelihood, software for the traveling salesman problem produces RH maps with better quality much more quickly than using software specifically tailored for RH mapping. We use known algorithms for the longest common subsequence problem as part of our map integration strategy. We demonstrate our methods by reconstructing and integrating maps for markers typed on the Genebridge 4 (GB4) and the Stanford G3 panels publicly available from the RH database. We compare map quality of our integrated map with published maps for GB4 panel and G3 panel by considering whether markers occur in the same order on a map and in DNA sequence contigs submitted to GenBank. We find that all of the maps are inconsistent with the sequence data for at least 50% of the contigs, but our integrated maps are more consistent. The map integration strategy not only scales to multiple RH maps but also to any maps that have comparable criteria for measuring map quality. Our software improves on current technology for doing RH mapping in areas of computation time and algorithms for considering a large number of markers for mapping. The essential impediments to producing dense high-quality RH maps are data quality and panel size, not computation.

Algorithms↗
PubMed1999

Towards a complete North American Anabaptist genealogy: A systematic approach to merging partially overlapping genealogy resources.

Genetic studies on closed populations benefit from comprehensive, searchable genealogy resources. To support studies of Anabaptists, a computerized database has been developed that merges two large genealogy books, the "Fisher Family History" and the "Amish and Amish Mennonite Genealogies." The former is more current but the latter is more comprehensive for the 18th and 19th centuries. Therefore, the merger of the two books is significantly more useful than either book alone. We demonstrate the utility of the merged database with two results: an increase in inbreeding coefficients and the identification of parent-child relationships that do not exist in either book. Am. J. Med. Genet. 86:156-161, 1999. Published 1999 Wiley-Liss, Inc.

Consanguinity↗
PubMed1999

The Sox10(Dom) mouse: modeling the genetic variation of Waardenburg-Shah (WS4) syndrome.

Hirschsprung disease (HSCR) is a multigenic neurocristopathy clinically recognized by aganglionosis of the distal gastrointestinal tract. Patients presenting with aganglionosis in association with hypopigmentation are classified as Waardenburg syndrome type 4 (Waardenburg-Shah, WS4). Variability in the disease phenotype of WS4 patients with equivalent mutations suggests the influence of genetic modifier loci in this disorder. Sox10(Dom)/+ mice exhibit variability of aganglionosis and hypopigmentation influenced by genetic background similar to that observed in WS4 patients. We have constructed Sox10(Dom)/+ congenic lines to segregate loci that modify the neural crest defects in these mice. Consistent with previous studies, increased lethality of Sox10(Dom)/+ animals resulted from a C57BL/6J locus(i). However, we also observed an increase in hypopigmentation in conjunction with a C3HeB/FeJLe-a/a locus(i). Linkage analysis localized a hypopigmentation modifier of the Dom phenotype to mouse chromosome 10 in close proximity to a previously reported modifier of hypopigmentation for the endothelin receptor B mouse model of WS4. To evaluate further the role of SOX10 in development and disease, we have performed comparative genomic analyses. An essential role for this gene in neural crest development is supported by zoo blot hybridizations that reveal extensive conservation throughout vertebrate evolution and by similar Northern blot expression profiles between mouse and man. Comparative sequence analysis of the mouse and human SOX10 gene have defined the exon-intron boundaries of SOX10 and facilitated mutation analysis leading to the identification of two new SOX10 mutations in individuals with WS4. Structural analysis of the HMG DNA-binding domain was performed to evaluate the effect of human mutations in this region.

Amino Acid Sequence↗
PubMed1998

Genetic and physical mapping of the McKusick-Kaufman syndrome.

McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos. This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894 , an area that includes the Alagille syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease-causing mutations.

Abnormalities, Multiple↗
PubMed1998

Software for constructing and verifying pedigrees within large genealogies and an application to the Old Order Amish of Lancaster County.

This paper describes PedHunter, a software package that facilitates creation and verification of pedigrees within large genealogies. A frequent problem in medical genetics is to connect distant relatives with a pedigree. PedHunter uses methods from graph theory to solve two versions of the pedigree connection problem for genealogies as well as other pedigree analysis problems. The pedigrees are produced by PedHunter as files in LINKAGE format ready for linkage analysis. PedHunter uses a relational database of genealogy data, with tables in specified format, for all calculations. The functionality and utility of PedHunter are illustrated by examples using the Amish Genealogy Database (AGDB), which was created for the Old Order Amish community of Lancaster County, Pennsylvania.

Christianity↗
PubMed1997

Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model.

We consider the problem of determining the three-dimensional folding of a protein given its one-dimensional amino acid sequence. We use the HP model for protein folding proposed by Dill (1985), which models protein as a chain of amino acid residues that are either hydrophobic or polar, and hydrophobic interactions are the dominant initial driving force for the protein folding. Hart and Istrail (1996a) gave approximation algorithms for folding proteins on the cubic lattice under the HP model. In this paper, we examine the choice of a lattice by considering its algorithmic and geometric implications and argue that the triangular lattice is a more reasonable choice. We present a set of folding rules for a triangular lattice and analyze the approximation ratio they achieve. In addition, we introduce a generalization of the HP model to account for residues having different levels of hydrophobicity. After describing the biological foundation for this generalization, we show that in the new model we are able to achieve similar constant factor approximation guarantees on the triangular lattice as were achieved in the standard HP model. While the structures derived from our folding rules are probably still far from biological reality, we hope that having a set of folding rules with different properties will yield more interesting folds when combined.

Algorithms↗
PubMed1995

Fast algorithms for inferring evolutionary trees.

We present algorithms for the perfect phylogeny problem restricted to binary characters. The first algorithm is faster than a previous algorithm by Gusfield when the input matrix for the problem is sparse. Next, we present two online algorithms. For the first of these, the set of species is fixed and the characters are given as input one at a time, while, for the second, the set of characters is fixed and the species are given as input one at a time. These two online algorithms are then combined into an algorithm that can process any sequence of additions and deletions of species and characters.

Algorithms↗
PubMed1992

Can mitral regurgitation after balloon dilatation of the mitral valve be predicted?

OBJECTIVE: To determine which factors predict the occurrence of mitral regurgitation after balloon dilatation of the mitral valve for rheumatic stenosis. DESIGN: Analysis of a case series of patients with rheumatic mitral valve stenosis who had had successful balloon dilatation of the mitral valve. SETTING: A tertiary care centre with an experience of over 150 balloon dilatations of the mitral valve. PATIENTS: 70 young patients with non-calcified rheumatic mitral stenosis, who had undergone successful balloon dilatation of the mitral valve. No patient had mitral regurgitation or atrial fibrillation before dilatation. INTERVENTION: Dilatation of the mitral valve by the transvenous, transatrial double balloon technique. MAIN OUTCOME MEASURE: Development of mitral regurgitation after balloon dilatation of the mitral valve and its relation to age, mitral valve area before dilatation and after dilatation, the degree of mitral subvalvar pathology, and the size of balloon used for dilatation. RESULTS: In 10 patients (14%) mitral regurgitation developed after balloon dilatation of the mitral valve. No statistically significant differences were found between patients who did not develop regurgitation and those who did in terms of age (mean (SD)) (19.9 (6.46) v 19.4 (5.5)), mitral valve area before dilatation (1.05 (0.33) v 0.94 (0.4) cm2) and after dilatation (2.52 (1.06) v 2.45 (1.1) cm2), mitral subvalvar pathology assessed by the mitral subvalvar distance ratio (0.116 (0.03) v 0.118 (2.32), or balloon diameter corrected for body surface area (21.37 (3.5) v 20.57 (2.32) mm/m2. CONCLUSIONS: In this subset of children and young adults with non-calcified mitral stenosis, none of the morphological, technical, or patient characteristics studied predicted the development of mitral regurgitation after balloon dilatation. The low incidence of mitral regurgitation may have reduced the discriminatory power of this study. None the less, the means and standard deviation for each factor in each group suggest that even in a larger sample size the variables would have little predictive capacity.

Adolescent↗
PubMed1991

Double outlet left ventricle with intact ventricular septum: a cross-sectional and Doppler echocardiographic diagnosis.

Double outlet left ventricle with intact ventricular septum, valvar pulmonary stenosis, an atrial septal defect within the oval fossa, dysplastic tricuspid valve and normally related great arteries are described in a four-year old male child presenting with cyanosis since birth. The diagnosis was made by cross-sectional and Doppler echocardiography and confirmed by cineangiocardiography.

Angiocardiography↗
PubMed1990

A study of aluminum phosphide (AlP) poisoning with special reference to electrocardiographic changes.

Ninety patients with aluminum phosphide poisoning have been studied over a period of 3 years. Epigastric pain and vomiting were the common initial clinical features, followed 12 to 24 hours later by cardiogenic shock, oliguria, altered mental state and respiratory distress. Death occurred within 24 to 72 hours presumably due to poison-induced toxic chemical myocarditis as reflected by electrocardiographic changes. The overall mortality was 63.3%. Intravenous magnesium sulphate, probably due to its membrane stabilizing action, appears to be related to the reduction in mortality from 90% to 52% in the latter 62 cases.

Adolescent↗