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Biomedical subjects

J N Bailey

Publications and source records attributed to J N Bailey.

15 recordsLinked to original sources
PubMed2001

SNPing away at candidate genes.

We develop regression methodology to identify subsets of single nucleotide polymorphisms (SNPs) within candidate genes related to quantitative traits and apply our methods to the simulated Genetic Analysis Workshop (GAW) 12 data set. In the data set we find 694 SNP loci with minimum allele frequencies of at least 0.01. We assume an additive casual model between these SNPs and all five quantitative traits. After initial screening using one-way analysis of variance, we employ a computationally efficient, simulated annealing algorithm to select among all possible subsets of SNP loci, using a generalization of Mallows' Cp as our optimality criterion. The simple transition kernel we develop evaluates new subsets in O(1), by requiring just three arithmetic operations to calculate the proposed RSS based on the Gauss-Jordan pivot. We identify an SNP loci located at 6-5782 related to traits 2 and 3 and several sites on gene 2 related to trait 5 using a subsample of 1,000 individuals and the full data set (n = 8,250) for comparison.

Alleles↗
PubMed2000

Macrocephaly in autism and other pervasive developmental disorders.

To assess the prevalence of macrocephaly (head circumference > or = 1.88 standard deviations above normative data for age and sex or > 97th centile) in autism and other pervasive developmental disorders, 41 children with autism, and a comparison group of 21 children with tuberous sclerosis complex (TSC) or an unspecified seizure disorder were studied. Familiality of head circumference was also assessed from measurements of 133 first-degree relatives. Significantly higher rates of macrocephaly were found in probands with autism (12.2%) and their first-degree relatives (15.5%) when compared against a published normative sample. The incidence of macrocephaly in the comparison group of probands with TSC and seizure disorder (9.5%) and their first-degree relatives (8.3%) was higher than normative data as well, although the relation between macrocephaly and autism was more pronounced. Head circumference and extreme scores reflecting macrocephaly were moderately heritable in the present sample (H2 = 0.47). The increased prevalence of macrocephaly in relatives of children with autism compared with control children suggests that this characteristic may be a familial risk factor in the pathogenesis of autism.

Adolescent↗
PubMed1999

Search for a gene x environment interaction: G x E hunt.

We developed a method to identify gene x environment interactions (G x Es). To test this method in the simulated data (Problem 2, GAW11), we first identified an environmental factor (E1) that was associated with the simulated disorder. We stratified affected sibling pairs (ASPs) into two groups, those concordant for the presence of E1 and those concordant for the absence of E1. We then localized genes on chromosomes 3 and 5 using identity-by-descent (IBD) sharing rates among ASPs. Because the stratified IBD sharing rates are independent of the environmental factor if there is no G x E, we inferred the existence of a G x E near loci 3G44 and 3G45 by testing whether the proportion of ASPs sharing no alleles IBD differed among the two groups.

Environment↗
PubMed1999

Transmission of primary nocturnal enuresis and attention deficit hyperactivity disorder.

Primary nocturnal enuresis (PNE) is a prevalent disorder among children with a complex mode of inheritance. Family, twin, and linkage studies have provided evidence that genetic factors underlie the familiality of PNE. Linkage investigations support the hypothesis that PNE is heterogeneous, and the genetic heterogeneity may be reflected in co-morbid clinical conditions such as attention deficit hyperactivity disorder (ADHD). This study used a family study method and examined the transmission of PNE in relatives of PNE and control probands with and without ADHD, to determine if these disorders co-occur due to common genetic susceptibilities or other, i.e. non-genetic, reasons. This study concluded that the pattern of inheritance found is consistent with the independent transmission of PNE and ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral problem afflicting 5-10% of children and adolescents and persisting into adulthood in 30-50% or more of cases. Family, twin, and adoption studies suggest genetic factors contribute to ADHD and symptoms of inattention, impulsivity, and hyperactivity. Because stimulant intervention is effective in reducing ADHD symptoms in about 70-80% of cases, molecular genetic investigations of genes involved in dopamine regulation are currently underway by many groups. In a case control study of the dopamine D4 receptor gene (DRD4) and ADHD, La Hoste and colleagues found an increase of a 7-repeat variant of a 48-bp VNTR in exon 3 among ADHD subjects compared to controls. Swanson and colleagues replicated this finding in a sample of 52 ADHD probands and their biological parents using a haplotype relative risk analysis. Here, we describe linkage investigations of the VNTR and ADHD in affected sibling pair (ASP) families and singleton families using both the transmission disequilibrium test (TDT) and a mean test of identity-by-descent (IBD) sharing. Using the TDT in the total sample, the 7 allele is differentially transmitted to ADHD children (P = 0.03) while the mean test revealed no evidence of increased IBD sharing among ASPs. In the current sample, the 7 allele attributes a 1.5-fold risk for developing ADHD over non-carriers of the allele estimated under a model described by Risch and Merikangas.

Adult↗
PubMed1997

A multivariate approach to affected-sib-pair analysis using highly dense molecular maps.

A multivariate approach to affected-sib-pair analyses was performed to localize disease-susceptibility genes with a minimum number of type I errors (false positives). Using 1,155 independent affected sib pairs extracted from Problem 2A of the GAW10 data set, we were able to localize major genes (MG) 1 and 2. Using 30% of the affected-sib-pair sample (N = 337) we were able to localize MG1. False positives were not detected in either of these samples.

Computer Simulation↗
PubMed1995

Complex segregation analyses of old order Amish families ascertained through bipolar I individuals.

Specific genetic hypotheses about the mode of transmission of bipolar affective disorders were examined by performing complex segregation analyses of Old Order Amish families. The analyses were performed on 1) the total set of 42 families including 689 relatives, 2) a subset of 19 families consisting of those kindreds sharing common ancestors within three generations that contained 333 relatives, and 3) a subset of 23 more distantly related families with 356 relatives. When all 42 families were included in the analyses, the specific mode of transmission that could be distinguished was dependent upon the diagnostic scheme used in the analysis. An autosomal dominant mode of inheritance could be rejected when relatives with bipolar I, atypical bipolar, major depressive disorder, and hypomania were included as affected. When analyses included only the subset of families more closely related, an autosomal dominant inheritance model was found to be consistent with transmission of BP I disorder. It was not possible to distinguish between other transmission models with broader diagnostic schemes in this subset of families. Finally, results of analyses on the subset of more distantly related families suggest that there is a significant proportion of Old Order Amish families in which the genetic factors contributing to the expression of bipolar illness are either polygenic or oligogenic.

Adolescent↗
PubMed1995

A brute force dichotomization approach to quantitative trait linkage analysis.

The effect of dichotomizing a continuous phenotype in linkage analysis of a simulated oligogenic trait is explored. We conclude that dichotomization does not in itself preclude the detection of loci which account for as little as 16% of the genetic variance of the disease. The effects of inclusion of known covariates and quantitative trait linkage analysis are also discussed.

Genetic Diseases, Inborn↗
PubMed1985

Sequence and analysis of the gene for bacteriophage T3 RNA polymerase.

The RNA polymerases encoded by bacteriophages T3 and T7 have similar structures, but exhibit nearly exclusive template specificities. We have determined the nucleotide sequence of the region of T3 DNA that encodes the T3 RNA polymerase (the gene 1.0 region), and have compared this sequence with the corresponding region of T7 DNA. The predicted amino acid sequence of the T3 RNA polymerase exhibits very few changes when compared to the T7 enzyme (82% of the residues are identical). Significant differences appear to cluster in three distinct regions in the amino-terminal half of the protein. Analysis of the data from both enzymes suggests features that may be important for polymerase function. In particular, a region that differs between the T3 and T7 enzymes exhibits significant homology to the bi-helical domain that is common to many sequence-specific DNA binding proteins. The region that flanks the structural gene contains a number of regulatory elements including: a promoter for the E. coli RNA polymerase, a potential processing site for RNase III and a promoter for the T3 polymerase. The promoter for the T3 RNA polymerase is located only 12 base pairs distal to the stop codon for the structural gene.

Amino Acid Sequence↗
PubMed1983

Relationship between promoter structure and template specificities exhibited by the bacteriophage T3 and T7 RNA polymerases.

To explore the basis for the template specificities of the bacteriophage T3 and T7 RNA polymerases (EC 2.7.7.6), we determined the nucleotide sequences of six promoters recognized by the T3 RNA polymerase and compared them with the previously determined promoter sequences recognized by the bacteriophage T7 RNA polymerase. Recombinant plasmids containing random Hpa II and Taq I fragments of T3 DNA were screened for T3 promoter activity in vitro in a transcription assay using purified T3 RNA polymerase. Five promoters for the T3 RNA polymerase were identified in this manner and their sequences were determined; the sequence of an additional promoter was determined directly from a genomic DNA fragment. In five of the T3 promoters an identical 16-base-pair sequence (A-C-C-C-T-C-A-C-T-A-A-A-G-G-G-A) extends from -12 to +4 (initiation occurring with GTP at +1); this sequence is preceded by a 6-base-pair A + T region. The remaining promoter contains an inserted C at position -1 and an A at the +1 position. The sequence of the 5' end of the RNA transcript from the latter promoter confirms that transcription is initiated with ATP at the +1 position. Previously, late T3 or T7 transcripts had not been found to initiate with ATP. The highly conserved T3 promoter sequence was compared to the T7 promoter consensus sequence. The fundamental difference between the two kinds of phage promoters is the occurrence of G-A at positions -11 and -10 in the T7 promoter, whereas there is a single C at position -10 in the T3 promoter.

Base Sequence↗
PubMed1980

Mapping of promoter sites utilized by T3 RNA polymerase on T3 DNA.

Promoter locations for the T3 RNA polymerase on the physical map of T3 DNa have been determined. Through the use of conditions favoring the synthesis of RNA from the class II region, an agarose-formaldehyde gel system which improves the resolution of high molecular weight RNAs, and template DNA that was cut by one of several restriction endonucleases prior to transcription, seventeen promoter locations for the T3 RNA polymerase have been mapped. Ten promoters have been identified in the class II region and one promotor has been identified in the class II region and one promotor has been identified in the early (class I) region. The locations of previously mapped class III promoters and the internal termination signal for the T3 RNA polymerase have been mapped more precisely than in previous reports. The resulting transcription map demonstrates a striking similarity to the transcription map of bacteriophage T7.

Binding Sites↗
PubMed1980

Derivation of a restriction map of bacteriophage T3 DNA and comparison with the map of bacteriophage T7 DNA.

The DNA of bacteriophage T3 was characterized by cleavage with seven restriction endonucleases. AvaI, XbaI, BglII, and HindIII each cut T3 DNA at 1 site, KpnI cleaved it at 2 sites, MboI cleaved it at 9 sites, and HpaI cleaved it at 17 sites. The sizes of the fragments produced by digestion with these enzymes were determined by using restriction fragments of T7 DNA as molecular weight standards. As a result of this analysis, the size of T3 DNA was estimated to be 38.74 kilobases. The fragments were ordered with respect to each other and to the genetic map to produce a restriction map of T3 DNA. The location and occurrence of the restriction sites in T3 DNA are compared with those in the DNA of the closely related bacteriophage T7.

Base Sequence↗