Defining the regions of homology between human chromosome 16p12--13 and mouse chromosomes

In this study, the evolutionary relationship between human chromosome 16p12-p13 and mouse chromosomes was investigated by determining the order of marker loci in the region and then identifying the chromosomal locations of the homologous loci in mice. Eighteen genes from human 16 were mapped to fifteen subchromosomal regions by a variety of mapping approaches.^ Thirteen of the genes were mapped in the mouse. Linkage analysis with backcross mice and segregation analysis in a mouse - Chinese Hamster Ovary (CHO) somatic cell hybrid panel informative for different regions of mouse genome were used. The results assigned the thirteen genes to three different mouse chromosomes.^ A group of six genes on mouse 16 was found to be closely linked to Scid. The order of Myh11 and Mrp remains ambiguous since no recombination was detected in backcross analysis. Their relative position in human is also uncertain since they were shown to be very close to each other. For the other mouse loci, an unambiguous gene order could be determined and was found to be identical to that in human. Therefore, they comprise a new conserved linkage group between the two species. The orientation of the group was inverted relative to the centromeres, i.e. the proximal loci in one species become distal in another. The size of the group was estimated to be from 4.4 to 8 Mb and 10 to 32 cM in human. In mouse, it was about 21 cM in the backcross analysis. The two boundaries of the conserved linkage were defined within a 1 Mb range. It is now possible to predict the locations of mouse homologs for some human disease genes based on their locations on human 16p.^ The six human 16p genes that map to MMU7 showed a different gene order in mouse than in human. No recombination was found between Crym and Umod while Crym was distal to D16S79A and proximal to D16S92. The location of Stp and Cdr2 with respect to the above four loci was not determined since they were not mapped in the same set of backcross mice. These genes greatly expanded an existing conserved synteny group between the human 16p12-p13 region and the MMU7. It now consists of eleven loci that span a region of probably more than 10 Mb in human. The gene order derived from this study provided further evidence for chromosomal rearrangements within the conserved synteny. (Abstract shortened by UMI.) ^

The role of specific regions of ribosomal RNAs in translation termination

The ribosome is a molecular machine that produces proteins in a cell. It consists of RNAs (rRNAs) and proteins. The rRNAs have been implicated in various aspects of protein biosynthesis supporting the idea that they function directly in translation. In this study the direct involvement of rRNA in translation termination was hypothesized and both genetic and biochemical strategies were designed to test this hypothesis. As a result, several regions of rRNAs from both ribosomal subunits were implicated in termination. More specifically, the mutation G1093A in an RNA of the large subunit (23S rRNA) and the mutation C1054A in the small subunit RNA (16S rRNA) of the Escherichia coli ribosome, were shown to affect the binding of the proteins that drive termination, RF1 and RF2. These mutations also caused defects in catalysis of peptidyl-tRNA hydrolysis, the last step of termination. Furthermore, the mutations affected the function of RF2 to a greater extent than that of RF1, a striking result considering the similarity of the RFs. The major defect in RF2 function was consistent with in vivo characteristics of the mutants and can be explained by the inability of the mutant rRNA sites to activate the hydrolytic center, that is the catalytic site for peptidyl-tRNA hydrolysis. Consistent with this explanation is the possibility of a direct interaction between the G1093-region (domain II of 23S rRNA) and the hydrolytic center (most likely domains IV–VI of 23S rRNA). To test that interaction hypothesis selections were performed for mutations in domains IV–VI that compensated for the growth defects caused by G1093A. Several compensatory mutations were isolated which not only restored growth in the presence of G1093A but also appeared to compensate for the termination defects caused by the G1093A. Therefore these results provided genetic evidence for an intramolecular interaction that might lead to peptidyl-tRNA hydrolysis. Finally, a new approach to the study of rRNA involvement in termination was designed. By screening a library of rRNA fragments, a fragment of the 23S rRNA (nt 74-136) was identified that caused readthrough of UGA. The antisense RNA fragment produced a similar effect. The data implicated the corresponding segment of intact 23S rRNA in termination. ^

Descriptive epidemiology of cancer in three regions of Kazakhstan

The current study investigated data quality and estimated cancer incidence and mortality rates using data provided by Pavlodar, Semipalatinsk and Ust-Kamenogorsk Regional Cancer Registries of Kazakhstan during the period of 1996–1998. Assessment of data quality was performed using standard quality indicators including internal database checks, proportion of cases verified from death certificates only, mortality:incidence ratio, data patterns, proportion of cases with unknown primary site, proportion of cases with unknown age. Crude and age-adjusted incidence and mortality rates and 95% confidence intervals were calculated, by gender, for all cancers combined and for 28 specific cancer sites for each year of the study period. The five most frequent cancers were identified and described for every population. The results of the study provide the first simultaneous assessment of data quality and standardized incidence and mortality rates for Kazakh cancer registries. ^

A comparison of healthcare access, healthcare utilization and asthma self-management for Hispanic children in border and non-border regions of Texas

The purpose of this culminating experience was to investigate the relationships between healthcare utilization, insurance coverage, and socioeconomic characteristics of children with asthma along the Texas-Mexico Border. A secondary data analysis was conducted on cross-sectional data from the Texas Child Asthma Call-back Survey, a follow-up survey to the random digit dialed Behavior Risk Factor Surveillance Study (BRFSS) conducted between 2006-2009 ( n = 556 adults living in households with a child with asthma).^ The proportion of Hispanic children with asthma in Border areas of Texas was more than twice that of non-Border areas (84.8% vs. 28.8%). Parents in Border areas were less likely to have their own health insurance (OR = 0.251, 95% C.I. = 0.117-0.540) and less likely to complete the survey in English than Spanish (OR = 0.251 95% C.I. = 0.117-0.540) than parents in non-Border areas. No significant socio-economic or health care utilization differences were noted between Hispanic children living in Border areas compared to Hispanic children living in non-Border areas. Children with asthma along the Texas-Mexico Border, regardless of ethnicity and language, have insurance coverage rates, reported cost barriers to care, symptom management, and medication usage patterns similar to those in non-Border areas. When compared to English-speakers, Spanish-speaking parents in Texas as a whole are far less likely to be taught what to do during an asthma attack (50.2% vs. 78.6%).^ Language preference, rather than ethnicity or geographical residence, played a larger role on childhood asthma-related health disparities for children in Texas. Spanish-speaking parents in are less likely to receive adequate asthma self-management education. Investigating the effects of Hispanic acculturation rates and incongruent parent-child health insurance coverage may provide better insight into the health disparities of children along the Texas-Mexico Border.^

A trilocus sequence typing scheme for hospital epidemiology and subspecies differentiation of an important nosocomial pathogen, Enterococcus faecalis.

In this study, we present a trilocus sequence typing (TLST) scheme based on intragenic regions of two antigenic genes, ace and salA (encoding a collagen/laminin adhesin and a cell wall-associated antigen, respectively), and a gene associated with antibiotic resistance, lsa (encoding a putative ABC transporter), for subspecies differentiation of Enterococcus faecalis. Each of the alleles was analyzed using 50 E. faecalis isolates representing 42 diverse multilocus sequence types (ST(M); based on seven housekeeping genes) and four groups of clonally linked (by pulsed-field gel electrophoresis [PFGE]) isolates. The allelic profiles and/or concatenated sequences of the three genes agreed with multilocus sequence typing (MLST) results for typing of 49 of the 50 isolates; in addition to the one exception, two isolates were found to have identical TLST types but were single-locus variants (differing by a single nucleotide) by MLST and were therefore also classified as clonally related by MLST. TLST was also comparable to PFGE for establishing short-term epidemiological relationships, typing all isolates classified as clonally related by PFGE with the same type. TLST was then applied to representative isolates (of each PFGE subtype and isolation year) of a collection of 48 hospital isolates and demonstrated the same relationships between isolates of an outbreak strain as those found by MLST and PFGE. In conclusion, the TLST scheme described here was shown to be successful for investigating short-term epidemiology in a hospital setting and may provide an alternative to MLST for discriminating isolates.