A Recurrent Mutation in PARK2 Is Associated with Familial Lung Cancer

PARK2, a gene associated with Parkinson disease, is a tumor suppressor in human malignancies. Here, we show that c.823C>T (p.Arg275Trp), a germline mutation in PARK2, is present in a family with eight cases of lung cancer. The resulting amino acid change, p.Arg275Trp, is located in the highly conserved RING finger 1 domain of PARK2, which encodes an E3 ubiquitin ligase. Upon further analysis, the c.823C>T mutation was detected in three additional families affected by lung cancer. The effect size for PARK2 c.823C>T (odds ratio = 5.24) in white individuals was larger than those reported for variants from lung cancer genome-wide association studies. These data implicate this PARK2 germline mutation as a genetic susceptibility factor for lung cancer. Our results provide a rationale for further investigations of this specific mutation and gene for evaluation of the possibility of developing targeted therapies against lung cancer in individuals with PARK2 variants by compensating for the loss-of-function effect caused by the associated variation.     

Development of microsatellite markers for Qualea grandiflora (Vochysiaceae), a typical species of the Brazilian cerrado

? Premise of the study: Microsatellite primers were developed to investigate genetic diversity and population structure of Qualea grandiflora, a typical species of the Brazilian cerrado. ? Methods and Results: Eight microsatellite loci were isolated using an enrichment cloning protocol. These loci were tested on a population of 110 individuals of Q. grandiflora collected from a cerrado fragment in S?o Paulo State, Brazil. The loci polymorphism ranges from seven to 19 alleles and the average heterozygosity value is 0.568, while the average polymorphic information content is 0.799. ? Conclusions: The developed markers were found to be highly polymorphic, indicating their applicability to studies of population genetic diversity in Q. grandiflora.     

Molecular epidemiology of human immunodeficiency virus-1 in the state of Ceará, Northeast,Brazil

We analyzed, by env and gag heteroduplex mobility assay, 149 human immunodeficiency virus (HIV-1) positive samples collected in Ceará during the year 2000. The prevalence of subtype B was 81.2% and the prevalence of subtype F and B/F recombinants were both 2.7%. Eight (5.4%) and 12 (8%) out of 149 samples showed indeterminate results in the env and gag analysis respectively. By FokI restriction fragment length polymorphism, 34% of the subtype B samples were identified as the typical Brazilian subtype B.In the present study, we identified HIV-1 subtype F and B/F in Ceará for the first time. Our results contribute to the understanding of HIV in Brazil, and may prove useful for the development of vaccine candidates.     

Comparison of longitudinal variance components and regression-based approaches for linkage detection on chromosome 17 for systolic blood pressure

We compare two methods to detect genetic linkage by using serial observations of systolic blood pressure in pedigree data from the Framingham Heart Study focusing on chromosome 17. The first method is a variance components (VC) approach that incorporates longitudinal pedigree data, and the second method is a regression-based approach that summarizes all longitudinal measures in one single measure. No evidence of linkage was found either using the VC longitudinal approach or the regression-based approach, except when all time points were used from Cohorts 1 and 2 and only subjects aged 25 and 75 years were included.     

Restriction fragment length polymorphism and evolution of the mouse immunoglobulin constant region gamma loci

Genomic DNA from twelve laboratory mouse strains, in addition to 21 wild-derived strains belonging to different taxa (Mus musculus domesticus, Mus musculus musculus, Mus spretus, Mus macedonicus, a and Mus spicilegus) and four mouse strains that are evolutionarily more distant, were analyzed by Southern blot for polymorphism of the Ig heavy chain constant region isotype (Igh-C) and for the distribution of the duplicated Igh-1 (C2) haplotype. Distinct allelic forms of each Igh-C locus could be defined by restriction fragment length polymorphism (RFLP). In laboratory mouse strains RFLP proved to be more sensitive in the detection of Igh-4 (C1) alleles than serological methods. Taq I digestion allowed the definition of two alleles in the Igh-8 (C3) locus, which is absolutely conserved at the protein levels. More extensive RFLP could be found in wild strains belonging to the subgenus Mus and in the evolutionarily more distant Mus species belonging to other subgenera. In previous studies we have shown that the Igh-1 locus is duplicated in M. m. musculus subspecies. We now extend this observations to the wild mouse strains belonging to M. spicilegus and M. macedonicus species and to the evolutionarily more distant wild mouse strain Mus pahari (subgenus coelomys), which is thought to have diverged from domestic mice about 5 million years ago. In addition, we found a similar RFLP pattern in ten of 18 wild mice trapped in India, suggesting that the haplotype containing the two Igh-1-like genes, organized in tandem as distinct isotypes, is widely spread in natural populations. The evolution of murine Igh-C-encoded isotypes is also discussed. Correspondence to: P.-A. Cazenave.     

Family-based association study of matrix metalloproteinase-3 and -9 haplotypes with susceptibility to ischemic white matter injury

Susceptibility to ischemic damage to the subcortical white matter of the brain has a strong genetic basis. Dysregulation of matrix metalloproteinases (MMPs) contributes to loss of cerebrovascular integrity and white matter injury. We investigated whether sequence variation in the genes encoding MMP3 and MMP9 is associated with variation in leukoaraiosis volume, determined by magnetic resonance imaging, in non-Hispanic whites and African-Americans using family-based association tests. Seven hundred and fifty-six white and 671 African-American individuals from sibships ascertained through two or more siblings with hypertension were genotyped for 7 and 8 haplotype-tagging polymorphisms in the MMP3 and MMP9 genes, respectively. MMP3 sequence variation was significantly associated with variation in leukoaraiosis volume in Whites. Two common haplotypes with opposing relationships to leukoaraiosis volume were identified. MMP9 sequence variation was also significantly associated with variation in leukoaraiosis volume in both African-Americans and Whites. Different haplotypes contributed to these associations in the two racial groups. These findings add to the growing body of evidence from animal models and human clinical studies suggesting a role of MMPs in ischemic white matter injury. They provide the basis for further investigation of the role of these genes in susceptibility and/or progression to clinical disease.     

Archaeological Evidence of the Cultural Importance of <Emphasis Type="Italic">Agave spp</Emphasis>. in Pre-Hispanic Colima,Mexico

Archaeological Evidence of the Cultural Importance of Agave spp . in Pre-Hispanic Colima, Mexico. Production of agave-based food and fermented alcoholic beverages was highly relevant culturally and socially in pre-European contact western Mesoamerica. It has been hypothesized that agave distillation in western Mexico began in Colima in the early Colonial Era through adaptation of introduced Filipino techniques. Archaeological evidence is presented confirming the cultural and social significance of agave in Colima before contact, one of the fundamental conditions supporting this hypothesis. An analysis of circular subterranean stone structures in residential and ceremonial contexts (Classic and Postclassic periods: 200–1500 common era [CE]), and a comparison with stone ovens currently used to cook agave for the creation of spirits, indicate these structures were probably used for preparing food, including agave. Analysis of funerary ceramic vessel offerings with agave images (Colima phase: 400–600 CE) are reported for the first time. Their characteristics, and those of the associated burials and tombs, suggest those buried were agave growers or alcoholic beverage producers who fulfilled relevant roles in the society. Most of the agave images probably represent Agave angustifolia Lem and its cultivation. During the Colonial Era, the cultural and social relevance of agaves almost disappeared in Colima, possibly due to drastic reductions in the native human population, changing land use practices, and prohibitions against the production and sale of native alcoholic beverages.