High prevalence of chitotriosidase deficiency in Peruvian Amerindians exposed to chitin-bearing food and enteroparasites

The human genome encodes a gene for an enzymatically active chitinase (CHIT1) located in a single copy on Chromosome 1, which is highly expressed by activated macrophages and in other cells of the innate immune response. Several dysfunctional mutations are known in CHIT1, including a 24-bp duplication in Exon 10 causing catalytic deficiency. This duplication is a common variant conserved in many human populations, except in West and South Africans. Thus it has been proposed that human migration out of Africa and the consequent reduction of exposure to chitin from environmental factors may have enabled the conservation of dysfunctional mutations in human chitinases. Our data obtained from 85 indigenous Amerindians from Peru, representative of populations characterized by high prevalence of chitin-bearing enteroparasites and intense entomophagy, reveal a very high frequency of the 24-bp duplication (47.06%), and of other single nucleotide polymorphisms which are known to partially affect enzymatic activity (G102S: 42.7% and A442G/V: 25.5%). Our finding is in line with a founder effect, but appears to confute our previous hypothesis of a protective role against parasite infection and sustains the discussion on the redundancy of chitinolytic function

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Genic targets used for the identification of periodontal pathogens by PCR base methods

In the course of time the laboratory diagnosis of periodontal infection has been influenced by the difficulties encountered in the transport, growth and identification of the different pathogenic species involved in periodontal disease: species that form a complex biofilm on the subgengival plaque and require anaerobic conditions. The traditional cultural diagnostic method has been replaced by molecular ones (PCR), a technique able to identify the different species responsible for periodontal disease and which, in its real time PCR version, is also able to quantify the different bacteria species present in a sample. The core of the “PCR based method” procedure is represented by the in silico diagnostic system that includes: (i) a genetic target, representative of the single bacteria species under examination, (ii) oligonucleotides (primers and/or fluorescent probes) with optimal thermodynamic characteristics. Nevertheless, even though the methods available in the literature and from commercial kits provide procedures that are considered specific, sensitive and fast, they do not take into consideration the most important parameter of polymicrobial infection analysis: namely selectivity. The selectivity of a diagnostic test is represented not only by its ability to reveal low titles of a single pathogen species compared to high titles of other ones, but also by its capacity to point out simultaneously and with the same level of accuracy, the presence and/or the concentration of different microbial species. The purpose of this work is the description of the current sequences of nine different primary periodontal pathogens deposited in DNA Data Banks: Tannerella forsythensis, Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia, Fusobacterium nucleatum ssp, Camphylobacter gracilis, Prevotella nigriscens, Eichenella corrodens, Aggregatibacter actinomycetemcomitans and subsequently the in silico evaluation of the DNA regions characterized by a good selectivity