A5010680275- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Genetic Syndromes and Imprinting
- Gene expression and cancer classification
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- Prenatal Screening and Diagnostics
- Chromosomal and Genetic Variations
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Carcinogens and Genotoxicity Assessment
- Bioinformatics and Genomic Networks
- DNA Repair Mechanisms
- Tumors and Oncological Cases
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Radioactive contamination and transfer
- Biomedical Text Mining and Ontologies
- Cancer Diagnosis and Treatment
- Radioactivity and Radon Measurements
- Radiation Effects and Dosimetry
Western University
2014-2023
Cytodiagnostics (Canada)
2014-2023
Health Canada
2017
Washington Center
2016
University of Washington
1996-2016
University of Missouri–Kansas City
2001-2006
Children's Mercy Hospital
1999-2006
Committee on Publication Ethics
2004
Mercy Hospital
2003
Laboratory of Molecular Genetics
2003
CYP2B6 metabolizes many drugs, and its expression varies greatly. genotype-phenotype associations were determined using human livers that biochemically phenotyped for (mRNA, protein, activity), genotyped <i>CYP2B6</i> coding 5′-flanking regions. differed significantly between sexes. Females had higher amounts of mRNA (3.9-fold, <i>P</i> < 0.001), protein (1.7-fold, 0.009), activity (1.6-fold, 0.05) than did male subjects. Furthermore, 7.1% females 20% males poor metabolizers. Striking...
Abstract The selection of effective genes that accurately predict chemotherapy responses might improve cancer outcomes. We compare optimized gene signatures for cisplatin, carboplatin, and oxaliplatin in the same cell lines validate each signature using data from patients with cancer. Supervised support vector machine learning is used to derive sets whose expression related line GI 50 values by backwards feature cross-validation. Specific functional pathways distinguishing sensitive...
Prader—Willi syndrome is a genetic disorder characterized by infantile hypotonia, obesity, hypogonadism, and mental retardation, but it difficult to diagnose clinically in infants young children. In about two thirds of patients, cytogenetically visible deletion can be detected the paternally derived chromosome 15 (15q11q13). Recently, patients with have been described who do not cytogenetic instead copies 15q11q13 region that are inherited from mother (with none father). This unusual form...
Splice site nucleotide substitutions can be analyzed by comparing the individual information contents (Ri, bits) of normal and variant splice junction sequences [Rogan Schneider, 1995]. In present study, we related splicing abnormalities to changes in Ri values 111 previously reported 41 different genes. Mutant donor acceptor sites have significantly less than their counterparts. With one possible exception, primary mutant with <2.4 bits were not spliced. Sites ≥2.4 but corresponding natural...
Patients with disorders involving imprinted genes such as Angelman syndrome (AS) and Prader-Willi (PWS) can have a mutation in the imprinting mechanism. Previously, we identified an center (IC) within chromosome 15q11-ql3 proposed that IC mutations block resetting of imprint, fixing on parental imprint (epigenotype) which arose. We now describe four new microdeletions IC, smallest (6 kb) currently defines minimal region sufficient to confer AS mutation. The deletions all overlap this region,...
Information theory–based software tools have been useful in interpreting noncoding sequence variation within functional elements such as splice sites. Individual information analysis detects activated cryptic sites and associated splicing regulatory is capable of distinguishing null from partially alleles. We present a server (https://splice.cmh.edu) designed to analyze mutations binding either human genes, genome-mapped mRNAs, user-defined sequences, or dbSNP entries. Standard HUGO-approved...
<ns4:p>The interpretation of genomic variants has become one the paramount challenges in post-genome sequencing era. In this review we summarize nearly 20 years research on applications information theory (IT) to interpret coding and non-coding mutations that alter mRNA splicing rare common diseases. We compile spectrum published analyzed by IT, provide a broad perspective distribution deleterious natural cryptic splice site detected, as well those affecting regulatory sequences. Results for...
Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial remain unexplained. To determine whether some missing heritability is due to rare variants conferring high moderate risk, we tested for an association between c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 FANCM gene and cancer. An analysis genotyping data from 8635 cases 6625 controls different countries yielded [odds ratio (OR) = 3.93 (95%...
Recent studies have identified a new class of Prader-Willi syndrome (PWS) and Angelman (AS) patients who biparental inheritance, but neither the typical deletion nor uniparental disomy (UPD) or translocation. However, these DNA methylation throughout 15q11-q13, thus appear to mutation in imprinting process for this region. Here we describe detailed clinical findings five AS (three families) two PWS (one family). All essentially classical phenotype respective syndrome, except that incidence...
Mutations that affect mRNA splicing often produce multiple isoforms, resulting in complex molecular phenotypes. Definition of an exon and its inclusion mature relies on joint recognition both acceptor donor splice sites. This study predicts cryptic exon-skipping isoforms produced by mutations from the combined information contents (Ri, which measures binding-site strength, bits) distribution sites defining these exons. The total content (Ri,total) is sum Ri values sites, adjusted for...
BRCA1 and BRCA2 testing for hereditary breast ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including noncoding flanking sequences ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, XRCC2, identified 38,372 unique We apply information theory (IT) to predict prioritize variants uncertain significance regulatory,...
Two surfactant protein A (SP-A) genes and several alleles for each SP-A locus have been previously described. In this report we investigate the potential usefulness of loci as markers genetic studies. We establish conditions that allow identification with very similar sequences; also determine degree polymorphism locus: The heterozygosity information content (PIC) values SP-A1 are 0.63 0.55, respectively, SP-A2 0.50 0.56. course these studies, identify one new allele show in linkage...
To assess whether sleep abnormalities are related to the genetic in Prader-Willi Syndrome (PWS), we performed polysomnographic studies (nighttime and daytime) determined chromosome 15 genotypes eight patients with PWS. Four demonstrated onset REM periods (SOREM), five met objective criteria for severe or moderate excessive daytime sleepiness (EDS). Three of four SOREM displayed a paternally derived deletion 15q11-q13, whereas fourth exhibited maternal uniparental heterodisomy this...
The examination of preserved, organic archaeological remains with the techniques molecular genetics is providing direct access to genetic components these tissues. Although nucleic acids are often chemically modified and substantially sheared, it has been possible retrieve ancient DNA sequences. polymerase chain-reaction method, which overcome inhibitory properties lesion-containing DNA, capable reconstructing sequences from template molecules that shorter than amplified products. This made...
The aim of this study was to clarify the nature sleep abnormalities (excessive daytime sleepiness [EDS] and rapid eye movement [REM] alterations) in Prader-Willi, Syndrome (PWS). Eight PWS patients, 15 normal, 16 narcoleptic, obese subjects were recorded laboratory, both during nighttime. A principal-finding that EDS associated with an increased amount depth sleep. In patients EDS, compared those without or narcoleptic. obese, normal groups, there significant decreases wakefulness increases...
Somatic mutations reported in large-scale breast cancer (BC) sequencing studies primarily consist of protein coding mutations. mRNA splicing mutation analyses have been limited scope, despite their prevalence Mendelian genetic disorders. We predicted 442 BC tumour and matched normal exomes from The Cancer Genome Atlas Consortium (TCGA). These defects were validated by abnormal expression changes these tumours. Of the 5,206 putative identified, exon skipping, leaky or cryptic was confirmed...
<ns4:p>Genomic aberrations and gene expression-defined subtypes in the large METABRIC patient cohort have been used to stratify predict survival. The present study normalized expression signatures of paclitaxel drug response outcome for different survival times patients receiving hormone (HT) and, some cases, chemotherapy (CT) agents. This machine learning method, which distinguishes sensitivity vs. resistance breast cancer cell lines validates predictions patients; was also derive other HT...
Dose from radiation exposure can be estimated dicentric chromosome (DC) frequencies in metaphase cells of peripheral blood lymphocytes. We automated DC detection by extracting features Giemsa-stained images and classifying objects machine learning (ML). involves (i) intensity thresholded segmentation objects, (ii) separation watershed transformation elimination inseparable clusters, fragments staining debris using a morphological decision tree filter, (iii) determination width centreline,...