The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the ...associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
The genus Anemone (Ranunculaceae) includes many species cultivated for ornamental purposes. Most cut flower cultivars belong to A. coronaria L. and are multiplied by seed and sold for cultivation as ...1-year-old tubers. As cultivars represent a population of hybrid individuals derived from crosses between heterozygous parents, the use of a true F₁ hybrid would improve the uniformity and quality of the product. As a first step towards the development of pure-breeding lines, anther cultures were established from elite cultivars of A. coronaria. Somatic embryos and plantlets were regenerated from five elite cultivars, and up to 16.9 regenerants per 100 cultured anthers were obtained. Cytological analysis identified that 11 of 19 regenerants had either a 2x = 16 karyotype, or were mixoploids. RAPD-based DNA fingerprinting showed that all the regenerants tested differed genetically from their anther donor, confirming their androgenetic origin. The shortening to 15 months for the time required to produce homozygous lines may convince seed companies to invest in F₁ hybrid breeding.
The existence of the previously reported intermetallic phases NiW and NiW2 is refuted on the basis of new experiments involving arc-melted samples. A careful study of the literature shows that these ...two phases were previously evidenced only in sintered alloys and in diffusion couples, both techniques being very prone to surface contamination. It is shown that the phase previously reported as NiW is in fact the low carbon containing ternary carbide Ni6W6C. The second phase NiW2 is most probably the higher ternary carbide Ni2W4C. This study raises also the question of the existence of the equiatomic phase appearing in the Fe-W phase diagram. A crystal structure Rietveld refinement of the intermediate phase Ni4W is also given in the present work, evidencing large substitutional disorder.
Objectives
To identify main prognostic factors for 5-year mortality among age-related comorbidities (ARCs) in older people living with HIV (PLHIV).
Design
A prospective, multicentre cohort study with ...a 5-year follow-up period in the late HAART era (from January 2008 to December 2012).
Setting
The Dat’AIDS cohort involving 12 French hospitals.
Participants
All actively followed HIV-1 infected patients aged 60 or older.
Measurements
The study endpoint was all-cause five-year mortality. The following ARCs were considered: chronic renal disease, cardiovascular diseases, cancer, chronic pulmonary disease, cirrhosis, diabetes and nutritional status. Hepatitis C (HCV), hepatitis B (HBV) co-infection and sociodemographic characteristics were also evaluated. Cox’s Proportional Hazards model was used for multivariate analysis.
Results
Among 1415 PLHIV aged 60 or more patients included, mean age was 66±5.5 years; 154 died (mortality rate 2.47/100 patientyears). The most prevalent ARCs were chronic renal disease (20.1%), diabetes (14.2%) and cardiovascular diseases (12.2%). By multivariate analysis, chronic renal disease (adjusted hazard ratio (aHR)=2.25; 95% confidence interval (CI) 1.58-2.21; p<10-4), cardiovascular diseases (aHR=2.40; 95%CI1.64-3.52; p<10-4), non-HIV related cancer (aHR=1.91; 95%CI1.20-3.05; p=0.007), cirrhosis (aHR=2.99; 95%CI1.68-5.33; p<10-3), HCV co-infection (aHR=2.00; 95%CI1.18-3.38; p=0.009), low body mass index (aHR=2.42; 95%CI1.46-4.01; p<10-3) and CD4 cell count < 200cells/
μ
l (aHR=2.23; 95%CI1.36-3.65; p=0.002) were independently associated with 5 year mortality.
Conclusion
Due to a high prevalence, chronic renal disease and cardiovascular disease are main prognostic factors for 5-year mortality among aged PLHIV.
Anemone coronaria is an out-crossing species grown widely as an ornamental. The genetic divergence between and within five widely commercialised cultivars ('Cristrina', 'Monalisa', 'Tetraelite', ...'Wicabri' and 'Mistral') has been evaluated using AFLP markers. Within each cultivar three-to-eight sub-cultivars, which differ mainly in the colour of their flowers, were assayed. Four plants within each sub-cultivar were genotyped. Due to the large size of the A. coronaria genome, an AFLP protocol based on restriction with Sbf I (an 8 bp cutter) and Mse I (a 4 bp cutter) was developed. Clear and reproducible electrophoretic patterns displaying 56 - 79 bands (average 67) per primer combination were obtained by applying five (Sbf I+2 / Mse I+3) selective nucleotides. A total of 402 bands were observed, of which 152 were polymorphic. Genetic similarities between accessions were calculated according to the Simple Matching Coefficient and used to construct a dendrogram based on the unweighted pair group method using arithmetic averages (UPGMA). The dendrogram resolved the entries into three major branches: A, which included sub-cultivars of 'Cristina'; B, which included two clusters grouping the sub-cultivars of 'Monalisa' and 'Mistral'; and C which included two clusters grouping the sub-cultivars of 'Tetraelite' and 'Wicabri'. The genetic relationships that emerged from our results are consistent with the known origins of these A. coronaria accessions.The majority of plants within each sub-cultivar clustered with one another, but in some cases, no clear genetic differentiation between sub-cultivars was detectable. Due to the high level of within-sub-cultivar genetic variation detected, future breeding strategies should be based on stabilising cultivars for agronomic and commercial characters, while simultaneously maintaining a high level of heterozygosity, in order to avoid inbreeding depression.
Large TSC gene rearrangements are not rare findings in tuberous sclerosis. Interestingly, all deletions, duplications and inversions so far described involve TSC2, none being associated with TSC1. In ...order to shed light on the structural basis of the preferential DNA rearrangements in TSC2 over TSC1 and to assess, in an unselected patient population, the prevalence of large re-arrangements in both TSC loci, we screened 202 tuberous sclerosis patients consecutively referred at our center. Southern blot analysis on EcoRI+HindIII double-digested DNA identified 19 partial or full-length gene deletions: three involved TSC1 and sixteen TSC2. The breakpoint sequence of seven internal deletions, three in TSC1 and four in TSC2, allowed us to speculate on the mechanism favoring TSC2 unequal recombinations and to identify a deletion hot spot that lies in TSC1 and that may be relevant in the routine genetic testing of tuberous sclerosis. Briefly, three major features appear to distinguish TSC1 from TSC2 deletions: (1) deletion size: all TSC1 deletions are within the transcriptional unit, whereas 12 of the 16 TSC2 deletions have at least one external breakpoint; (2) location within the gene: all TSC1 deletions are confined to the 3'end of the gene (all three 5' breakpoints being located in intron 20) thus resulting in the same frameshift mutation following amino acid K875, whereas the TSC2 internal breakpoints appear to be scattered along the gene; (3) preference for recombinatorial sequences: six out of eight internal TSC2 breakpoints map within Alu repeats, whereas none of the three TSC1 deletions appear to be Alu-mediated. Indeed, in the latter gene, unique structural features (a purine-rich tract flanked by pyrimidine-rich segments) surrounding one of the two identified breakpoint cluster regions might play a role in promoting inappropriate recombinations.
Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a ...previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers hazard ratio (HR) = 1.16, 95% CI: 1.07–1.25, P-trend = 2.8 × 10−4. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04–1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04–1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98–1.14) was consistent with odds ratio estimates derived from population-based case–control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.
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