Genetic markers for glutamic acid decarboxylase do not predict insulin-dependent diabetes mellitus in pairs of affected siblings

Reliable genetic and immunological markers are important in the prediction of insulin-dependent diabetes mellitus (IDDM). Since glutamic acid decarboxylase (GAD) is a candidate primary autoantigen, we examined the possible linkage between IDDM and the genes encoding GAD₆₅ (GAD2, 10p11–12) and GAD₆₇ (GAD1, 2q31) in 58 Danish IDDM affected sib pairs. The allelic inheritance of 10 polymorphic dinucleotide repeat sequences spanning the chromosomal regions of the two GAD genes, were examined by affected sib pair analysis (ASP). In addition a restriction fragment length polymorphism (RFLP) was identified in the gene encoding GAD₆₅ using the restriction enzyme PvuII. The GAD gene markers were analyzed in relation to the presence of specific HLA types and GAD autoantibodies. No evidence of linkage was found between IDDM and either of the genes encoding GAD. This was also the case when subgroups carrying specific HLA susceptibility alleles were analyzed. Nor did we observe any association between these GAD genetic markers and the presence of GAD autoantibodies. Considering the high prevalence of GAD autoantibodies in IDDM, a putative genetic association between GAD and IDDM would be expected to affect most diabetic individuals. Therefore, our data indicate that the association between GAD and IDDM is not genetically determined, and that microsatellites used in this study do not contribute to the prediction of IDDM. Received: 1 July 1996 / Revised: 21 August 1996     

Seasonal growth pattern of an Icelandic Laminaria population (section Simplices,Laminariaceae, Phaeophyta) containing solid- and hollow-stiped plants

Lamina elongation and content of mannitol, laminaran and nitrate were measured during one year in Laminaria saccharina sensu lato from Iceland. The population contained both solid- and hollow-stiped plants. Growth rate was at its minimum from October to December, and started to increase in mid-winter, slightly earlier at 3 m than at 5 m. The increase in growth rate coincided with a strong reduction in stored carbohydrates and an increase in nitrate content of the laminae, indicating that stored mannitol and laminaran provided extra energy for increased lamina growth and/or for nitrate uptake. The results showed that stored mannitol was utilised before laminaran. The growth rate was at its maximum from April to June, and was reduced from June to July. The ambient nitrate concentration at the locality was low from May to August. The nitrate content of the lamina tissue in relation to dry weight was high during spring but was reduced to low values by July, indicating that nitrate levels limited growth during summer. However, high nitrate concentration of the sea-water and high levels of storage carbohydrates in the plants during autumn indicate that the low growth rate at this time cannot be attributed to lack of nitrate or energy in the form of stored carbon. The Laminaria population in Iceland that was examined showed morphological similarity with L. longicruris populations in Canada (hollow stipe), while the growth pattern corresponds with European L. saccharina populations.     

Opportunities for Tuberculosis Diagnosis and Prevention among Persons Living with HIV: A Cross-Sectional Study of Policies and Practices at Four Large Ryan White Program-Funded HIV Clinics

Objective

We describe the frequency and attributes of tuberculosis testing and treatment at four publicly-funded HIV clinics.

Methods

We abstracted medical records from a random sample of 600 HIV-infected patients having at least one clinic visit in 2009 at four clinics in New York and Los Angeles Metropolitan Statistical areas. We described testing and treatment for tuberculosis infection (TBI), 2008–2010, and estimated adjusted odds ratios (aORs). We interviewed key informants and described clinic policies and practices.

Results

Of 600 patients, 500 were eligible for testing, and 393 (79%) were tested 2008–2010; 107 (21%) did not receive at least one tuberculin skin test or interferon gamma release assay. Results were positive in 20 (5%) patients, negative in 357 (91%), and unknown in 16 (4%). Fourteen (70%) of 20 patients with TBI initiated treatment at the clinics; only three were documented to have completed treatment. Three hundred twenty three (54%) patients had chest radiography, 346 (58%) had tuberculosis symptom screening, and three had tuberculosis disease (117 per 100,000 person-years, 95% confidence interval (CI) = 101–165). Adjusting for site, non-Hispanic ethnicity (aOR = 4.9, 95% CI = 2.6–9.5), and employment (aOR = 1.9, 95% CI = 1.0–3.4) were associated with TBI testing; female gender (aOR = 2.0, 95% CI = 1.4–3.3), non-black race (aOR = 1.7, 95% CI = 1.3–2.5), and unemployment (aOR = 1.5, 95% CI = 1.1–2.1) were associated with chest radiography. Clinics evaluated TBI testing performance annually and identified challenges to TB prevention.

Conclusions

Study clinics routinely tested patients for TBI, but did not always document treatment. In a population with a high TB rate, ensuring treatment of TBI may enhance TB prevention.     

Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS)

The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children''s Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188–5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals.     

Being abundant is not enough: a decrease in effective population size over eight generations in a Norwegian population of the seaweed, Fucus serratus

The brown alga Fucus serratus is a key foundation species on rocky intertidal shores of northern Europe. We sampled the same population off the coast of southern Norway in 2000 and 2008, and using 26 microsatellite loci, we estimated the changes in genetic diversity and effective population size (Ne). The unexpectedly low Ne (73-386) and Ne/N ratio (10-3-10-4), in combination with a significant decrease (14%) in allelic richness over the 8-year period, suggests an increased local extinction risk. If small Ne proves to be a common feature of F. serratus, then being abundant may not be enough for the species to weather future environmental changes.     

A multistage testing strategy for detection of quantitative trait Loci affecting disease resistance in Atlantic salmon

A multistage testing strategy to detect QTL for resistance to infectious salmon anemia (ISA) in Atlantic salmon is proposed. First, genotyping of amplified fragment length polymorphisms (AFLP) and a transmission disequilibrium test (TDT) were carried out using dead offspring from a disease resistance challenge test. Second, AFLP genotyping among survivors followed by a Mendelian segregation test was performed. Third, within-family survival analyses using all offspring were developed and applied to significant TDT markers with Mendelian inheritance. Maximum-likelihood methodology was developed for TDT with dominant markers to exploit linkage disequilibrium within families. The strategy was tested with two full-sib families of Atlantic salmon sired by the same male and consisting of 79 offspring in total. All dead offspring from the two families were typed for 64 primer combinations, resulting in 340 scored markers. There were 26 significant results out of 401 TDTs using dead offspring. In the second stage, only 17 marker families showed Mendelian segregation and were tested in survival analysis. A permutation test was performed for all survival analyses to compute experimentwise P-values. Two markers, aaccac356 and agccta150, were significant at P < 0.05 when accounting for multiple testing in the survival analyses. The proposed strategy might be more powerful than current mapping strategies because it reduces the number of tests to be performed in the last testing stage.     

Unravelling the complexity of salt marsh ‘Fucus cottonii’ forms (Phaeophyceae,Fucales)

Genetic affiliation, nuclear DNA content, and gamete functioning were examined in small salt marsh Fucus from three localities in western Ireland. Individuals with small and dioecious receptacles were found at all localities, but production of germlings was only evident at Locality 1. Here, the Fucus vegetation formed a morphological cline from F. vesiculosus with bladders in the mid-intertidal to small Fucus individuals lacking bladders in the salt marsh of the upper intertidal. Measurements of nuclear DNA content ranged from 1–1.8 pg at this locality, with F. vesiculosus individuals in the lower range. At the two other localities, the small salt marsh Fucus consisted of distinct morphological entities. Microsatellite analyses revealed that individuals at Locality 2 were derived mainly from F. vesiculosus, whereas those from Locality 3 were hybrids between F. vesiculosus and F. spiralis with greatest affiliation to F. spiralis. While the small salt marsh Fucus forms from Locality 2 had high nuclear DNA content (c. 4 pg) and were probably octoploids, the small salt marsh Fucus from Locality 3 formed two groups: one with high (3.9–4.6 pg) and one with low (1.5–1.9 pg) nuclear DNA content. Nuclear DNA content measured in individuals from Locality 3 varied between 1.1–2.8 pg in F. vesiculosus and 2–3.5 pg in F. spiralis, and showed a more or less stepwise increase in both species, consistent with polyploidy. We hypothesize that the small salt marsh Fucus forms originate from genome size changes in the parental taxa.     

Temporal and structural genetic variation in reindeer (Rangifer tarandus) associated with the pastoral transition in Northwestern Siberia

Just as the domestication of livestock is often cited as a key element in the Neolithic transition to settled, the emergence of large‐scaled reindeer husbandry was a fundamental social transformation for the indigenous peoples of Arctic Eurasia. To better understand the history of reindeer domestication, and the genetic processes associated with the pastoral transition in the Eurasian Arctic, we analyzed archaeological and contemporary reindeer samples from Northwestern Siberia. The material represents Rangifer genealogies spanning from 15,000 years ago to the 18th century, as well as modern samples from the wild Ta?myr population and from domestic herds managed by Nenetses. The wild and the domestic population are the largest populations of their kind in Northern Eurasia, and some Nenetses hold their domestic reindeer beside their wild cousins. Our analyses of 197 modern and 223 ancient mitochondrial DNA sequences revealed two genetic clusters, which are interpreted as representing the gene pools of contemporary domestic and past wild reindeer. Among a total of 137 different mitochondrial haplotypes identified in both the modern and archaeological samples, only 21 were detected in the modern domestic gene pool, while 11 of these were absent from the wild gene pool. The significant temporal genetic shift that we associate with the pastoral transition suggests that the emergence and spread of reindeer pastoralism in Northwestern Siberia originated with the translocation and subsequent selective breeding of a special type of animal from outside the region. The distinct and persistent domestic characteristics of the haplotype structure since the 18th century suggests little genetic exchange since then. The absence of the typical domestic clade in modern nearby wild populations suggests that the contemporary Nenets domestic breed feature an ancestry from outside its present main distribution, possibly from further South.