This study examined polymorphisms in the dihydrofolate reductase (DHFR) gene of Pneumocystis carinii isolates from 27 patients with P. carinii pneumonia (PCP) in Japan. Four substitution sites with two synonymous and two non-synonymous changes were found. Two synonymous substitutions at nucleotide positions 540 and 312 were identified in one and 13 patients, respectively. Two amino acid substit...

Artifactual evidence of adaptive amino acid substitution can be generated within a McDonald-Kreitman test if some amino acid mutations are slightly deleterious and there has been an increase in effective population size. Here I investigate the conditions under which this occurs. I show that fairly small increases in effective population size can generate artifactual evidence of positive selecti...

High-dose methotrexate is a standard component of therapy for high-grade osteosarcoma. Its effectiveness may be limited by intrinsic and acquired resistance. Decreased reduced folate carrier (RFC) expression has been shown in approximately half of osteosarcomas at diagnosis. Mutations and polymorphisms in the RFC gene have been reported in various cell lines. The purpose of this study was to in...

• Biophysical properties of residues: Amino acids differ in size and charge. Some are acidic, some are basic, some have aromatic side chains. Generally, replacement of an amino acid with another amino acid with similar properties is less likely to break the protein or cause a dramatic change in function than replacement with an amino acid with different properties. A substitution matrix should ...

To understand the role of CASP9 (Caspase-9) gene products in relation to neuroblastoma disease, we have analyzed the single nucleotide polymorphisms (SNPs) associated with this gene. This can help us understand the genetic variations that can alter the function of the gene products. A total of 941 SNPs are investigated for CASP9 gene. To determine whether a non-synonymous SNP (nsSNP) in this ge...

The selective forces acting on amino acid substitutions may be different in the two phases of molecular evolution: polymorphism and fixation. Negative selection and genetic drift may dominate the first phase, whereas positive selection may become much more significant in the second phase. However, the conventional dichotomy of synonymous vs. nonsynonymous changes does not offer the resolution n...

Introduction DNA repair helps to protect the genome from tobacco-induced damage. Reduced DNA repair capacity may predispose individuals to lung cancer (1). Polymorphisms in genes encoding DNA repair proteins may modulate susceptibility to tobacco lung carcinogens. Bulky DNA adducts induced by chemical carcinogens in cigarette smoke are repaired through the nucleotide excision repair pathway tha...

Tobacco use and alcohol consumption are the major risk factors for squamous cell carcinoma of the head and neck (SCCHN; ref. 1). Polymorphisms in tobacco carcinogen– and alcohol-metabolizing genes may contribute to variation in enzyme activities and, thus, influence individual susceptibility to SCCHN. Cytochrome P450 2E1 (CYP2E1) is a phase I enzyme that catalyzes metabolic activation of severa...

Mutations in the thymidine kinase (TK) gene of herpes simplex virus (HSV) have been associated with resistance to acyclovir (ACY) and possible recognition of neurotropic strains. We sequenced a 335-bp segment of the TK gene to determine the frequency of mutations in HSV strains recovered from dermal, genital, and cerebrospinal fluid (CSF) specimens (n = 200; 102 HSV type 1 [HSV-1] 98 HSV-2 stra...

β-amylase activity is related to the polymorphisms of Bmy1 intron III; however, no attention has been given such relationships under environmental stresses as drought. In this study, 73 cultivated barley genotypes and 52 Tibetan wild accessions were used test association between gene III drought stress. Our results showed that three alleles, Bmy1.a, Bmy1.b, Bmy1.c, existed in examined genotypes...