Telomerase activity and apoptosis genes as parameters of lymphocyte aging in Down syndrome patients

AbstractIt is hypothesized that Down syndrome (DS) patients are associated with abnormalities of the immune system. Accordingly, this study was conducted to measure replicative aging and apoptosis in lymphocytes, which play an important role in the immune system, before and after being biostimulated with He:Ne laser. Replicative aging was measured in terms of telomerase activity, and ETS-2 gene relative expression. Apoptosis was measured in terms of DNA fragmentation and apoptosis genes (Fas, FasL and Bax) and antiapoptotic Bcl-2 protein. Results showed that Telomerase activity, ETS-2 mRNA expression, plasma DNA fragmentation, Fas and FasL were significantly higher among DS patients compared to controls: Telomerase activity (1.5±0.5 vs. 0.9±0.4, p<0.001); ETS2 mRNA expression (0.6±0.1 vs. 0.43±0.04, p<0.0001); plasma DNA fragmentation (0.45%±0.12 vs. 0.2%±0.1, p<0.0001); Fas protein (5.3±1.2 vs. 2.3±0.2, p<0.0001); FasL mRNA relative expression (0.37±0.05 vs. 0.24±0.01, p<0.001); Bax mRNA relative expression (0.9±0.1 vs. 0.5±0.1, p<0.00001). Bcl-2 protein was significantly low in DS patients compared to controls (8.6±1.3 vs. 10±2.1, p<0.01). He:Ne laser biostimulation applied to evaluate lymphocytes’ response significantly increased the former parameters in DS patients compared to their level before irradiation, except for Bcl-2, which was significantly decreased. In conclusion: increased telomerase activity associated with increased activity and overexpression of ETS-2 on chromosome 21 in DS patients may contribute to the increased rate of early senescence in circulating lymphocytes, which consequently contributes to the abnormalities of the immune system observed in DS. Increased apoptosis is due to increased oxidative stress, which induces an increase in the apoptotic genes Bax, Fas and FasL accompanied by a decrease in the antiapoptotic gene Bcl-2

Schistosomal hepatic fibrosis and the interferon gamma receptor: a linkage analysis using single-nucleotide polymorphic markers

A minority of individuals infected with the parasite Schistosoma mansoni develops hepatic fibrosis. HLA studies in Egypt and a candidate gene search in a Sudanese population indicate that the host&apos;s genetics contribute to disease susceptibility. In an Egyptian community, 32.7% of individuals 11 years and older had significant fibrosis by WHO ultrasound criteria. Linkage to 10 candidate genes was tested using 89 affected sibling pairs from 40 pedigrees in this community. The candidates included genes that initiate fibrosis, participate in collagen synthesis, or control collagen degradation. Two to four single-nucleotide polymorphisms (SNPs) were genotyped per locus, and 188 individuals were genotyped at 48 markers. Model-free modified Haseman-Elston analysis identified linkage to a SNP in the interferon gamma receptor locus (P ¼ 0.000001). There was also weak evidence for linkage to the interleukin 13-4 region and tissue growth factor beta 1

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Population-based differences in Schistosoma mansoni- and hepatitis C-induced disease.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-04-30T17:46:05Z No. of bitstreams: 1 Blanton RE Population-Based....pdf: 102772 bytes, checksum: 506a414ee6f151ae09aded64abbda6a9 (MD5)Made available in DSpace on 2014-04-30T17:46:05Z (GMT). No. of bitstreams: 1 Blanton RE Population-Based....pdf: 102772 bytes, checksum: 506a414ee6f151ae09aded64abbda6a9 (MD5) Previous issue date: 2002Division of Geographic Medicine. Case Western Reserve University. Cleveland, OhioUniversity of Cairo. Department of Pediatrics. Cairo, EgyptDivision of Vector Borne Diseases. NairobiOffice of Radiologic Services. Kenya Ministry of Health. Nairobi, KenyaFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilDivision of Vector Borne Diseases. NairobiDivision of Vector Borne Diseases. NairobiUniversity of Cairo. Department of Pediatrics. Cairo, EgyptBiomedical Research and Training Institute. Harare, ZimbabweFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilDivision of Vector Borne Diseases. NairobiTwo populations with differing histories of Schistosoma mansoni and hepatitis C infection were compared directly for severity of disease and extent of comorbidity. Demographic, parasitologic, and ultrasound surveys were conducted on 2038 Egyptians and on 2120 Kenyans. Hepatitis B and C serologies and transaminase levels were obtained from a subset at each site. Despite significantly lower prevalence and intensity of infection, Egyptians had a higher prevalence of severe schistosomal fibrosis than Kenyans (36.8% vs. 4.6%). Hepatitis C infection was 3 times more prevalent among Egyptians, and evidence of hepatocellular damage was significantly greater among Egyptians. There was no interaction between S. mansoni infection or disease and the prevalence or severity of hepatitis C. For both infections, the intensity or prevalence of infection was a poor predictor of morbidity. The prevalence of disease in the Egyptian population from different pathogens suggests a generalized susceptibility to inflammatory liver disease