Grapevine Genetics: Probing the Past and Facing the Future

The development and application of DNA technology is changing the face of grapevine genetics. DNA markers facilitate investigations into the origins of existing cultivars and provide powerful tools for the creation of new cultivars. Microsatellite markers, the most powerful type of DNA markers, provide a unique genetic profile for every cultivar, permitting unambiguous identification that is unaffected by environment, disease or farming methods. Because they are locus-specific and co-dominant, microsatellite markers also detect family relationships and have revealed the origins of some of the world´s most important wine cultivars. For the first time, genetic linkage maps of grapevine are now being developed. The long generation time, large plant size, genetic heterozygosity and lack of conventional morphological genetic markers prohibited map development in the past. Now molecular marker based mapping programs are accelerating grape breeding programs by permitting early selection of promising seedlings. Genetic mapping in combination with physical mapping can lead to the isolation of grape genes that control important traits but for which the mechanism is not known. Other grape genes are being isolated by comparing expressed grape DNA sequences with large databases of well-characterized genes from other plants and animals. Methods to introduce genes, either from grapevines or other organisms, into existing grape cultivars are now well-established and permit the targeted modification of existing grape cultivars. This may provide a means to reduce disease losses and pesticide usage in classic cultivars without otherwise changing their wine attributes

Comparison of Vitis berlandieri x Vitis riparia rootstock cultivars by restriction fragment lenght polymorphism analysis

Patterns produced by RFLP analysis of genomic DNA extracted from nine Berlandieri ∞ riparia rootstock cultivars were compared. Of the six grape DNA probes used, several combinations of three probes were sufficient to clearly distinguish all nine rootstocks. Calculation of a similarity index for each pair revealed that 420 A was notably distinct from the other members of the group (D=0.56 compared to an average similarity of 0.77 among all the hybrids), while the Teleki hybrids (SO 4, 5 C, 5 BB, 125 AA, Cosmo 2, Cosmo 10) were generally very similar to each other (average D=0.85). No differences were observed between 5 A and 5 BB, consistent with previous reports that at least some 5 A vines are identical to 5 BB

Pregled istraživanja i literature vezanih uz porijeklo i identitet kultivara Plavac mali, Zinfandel i Primitivo (Vitis vinifera L.)

The origin of Zinfandel, the important California wine cultivar, has been a question for several decades. Although Zinfandel has been linked to both Primitivo, grown in southern Italy, and to Plavac mali in Croatia, the puzzle of its origin has never been solved. Many scientists and writers have applied themselves to this question. Many hypotheses have been proposed and some erroneous ideas have been widely accepted. Much of the controversy will now be ended as a result of recent scientific research (Pejić and co-workers, 2000). Here we review the research and written documentation about Plavac mali, Zinfandel and Primitivo and their relationships and we present the results of recent research.Porijeklo Zinfandela, važnog kalifornijskog vinskog kultivara, nepoznanica je više desetljeća. Iako je Zinfandel povezivan i sa Primitivom, koji se uzgaja u južnoj Italiji, i sa Plavcem malim u Hrvatskoj, zagonetka njegovog porijekla nikad nije riješena. Mnogi znanstvenici i pisci posvetili su se ovom pitanju. Predložene su mnoge hipoteze a neke krive ideje bivale su široko prihvaćene. Mnoge od kontroverzi trebale bi biti okončane nakon znanstvenog istraživanja Pejić i sur. (2000). U radu se iznosi pregled pisane dokumentacije o Plavcu malom, Zinfandelu i Primitivu i njihovoj povezanosti i iznose rezultati posljednjih istraživanja

Pregled istraživanja i literature vezanih uz porijeklo i identitet kultivara Plavac mali, Zinfandel i Primitivo (Vitis vinifera L.)

The origin of Zinfandel, the important California wine cultivar, has been a question for several decades. Although Zinfandel has been linked to both Primitivo, grown in southern Italy, and to Plavac mali in Croatia, the puzzle of its origin has never been solved. Many scientists and writers have applied themselves to this question. Many hypotheses have been proposed and some erroneous ideas have been widely accepted. Much of the controversy will now be ended as a result of recent scientific research (Pejić and co-workers, 2000). Here we review the research and written documentation about Plavac mali, Zinfandel and Primitivo and their relationships and we present the results of recent research.Porijeklo Zinfandela, važnog kalifornijskog vinskog kultivara, nepoznanica je više desetljeća. Iako je Zinfandel povezivan i sa Primitivom, koji se uzgaja u južnoj Italiji, i sa Plavcem malim u Hrvatskoj, zagonetka njegovog porijekla nikad nije riješena. Mnogi znanstvenici i pisci posvetili su se ovom pitanju. Predložene su mnoge hipoteze a neke krive ideje bivale su široko prihvaćene. Mnoge od kontroverzi trebale bi biti okončane nakon znanstvenog istraživanja Pejić i sur. (2000). U radu se iznosi pregled pisane dokumentacije o Plavcu malom, Zinfandelu i Primitivu i njihovoj povezanosti i iznose rezultati posljednjih istraživanja

Characterization of ten novel Ty1/copia-like retrotransposon families of the grapevine genome

BACKGROUND: Retrotransposons make a significant contribution to the size, organization and genetic diversity of their host genomes. To characterize retrotransposon families in the grapevine genome (the fourth crop plant genome sequenced) we have combined two approaches: a PCR-based method for the isolation of RnaseH-LTR sequences with a computer-based sequence similarity search in the whole-genome sequence of PN40024. RESULTS: Supported by a phylogenic analysis, ten novel Ty1/copia families were distinguished in this study. To select a canonical reference element sequence from amongst the various insertions in the genome belonging to each retroelement family, the following screening criteria were adopted to identify the element sequence with: (1) perfect 5 bp-duplication of target sites, (2) the highest level of identity between 5’ and 3’-LTR within a single insertion sequence, and (3) longest, un-interrupted coding capacity within the gag-pol ORF. One to eight copies encoding a single putatively functional gag-pol polyprotein were found for three families, indicating that these families could be still autonomous and active. For the others, no autonomous copies were identified. However, a subset of copies within the presumably non-autonomous families had perfect identity between their 5’ and 3’ LTRs, indicating a recent insertion event. A phylogenic study based on the sequence alignment of the region located between reverse transcriptase domains I and VII distinguished these 10 families from other plant retrotransposons. Including the previously characterized Ty1/copia-like grapevine retrotransposons Tvv1 and Vine 1 and the Ty3/gypsy-like Gret1 in this assessment, a total of 1709 copies were identified for the 13 retrotransposon families, representing 1.24% of the sequenced genome. The copy number per family ranged from 91-212 copies. We performed insertion site profiling for 8 out of the 13 retrotransposon families and confirmed multiple insertions of these elements across the Vitis genus. Insertional polymorphism analysis and dating of full-length copies based on their LTR divergence demonstrated that each family has a particular amplification history, with 71% of the identified copies being inserted within the last 2 million years. CONCLUSION: The strategy we used efficiently delivered new Ty1/copia-like retrotransposon sequences, increasing the total number of characterized grapevine retrotrotransposons from 3 to 13. We provide insights into the representation and dynamics of the 13 families in the genome. Our data demonstrated that each family has a particular amplification pattern, with 7 families having copies recently inserted within the last 0.2 million year. Among those 7 families with recent insertions, three retain the capacity for activity in the grape genome today

Relatedness of Cultivars Plavac Mali, Zinfandel and Primitivo (Vitis vinifera L.)

Pored svoje visoke kvalitete cv. Plavac mali poznat je u literaturi i kao mogući sinonim kultivara Zinfandel u Kaliforniji i kultivara Primitivo u Italiji. Hipoteza kako je Plavac mali zapravo autohtoni hrvatski kultivar (Dalmacija) prenesen u Italiju gdje dobiva ime Primitivo i u Kaliforniju gdje dobiva ime Zinfandel već ranije je znanstveno ispitivana. Komparacijom klimatskih zahtjeva za uzgoj i razvoj svakog od navedenih kultivara utvrdili smo da Plavac mali ne može biti istovjetni genotip ni kultivara Primitivo ni Zinfandel. Analizom biljega DNA (mikrosateliti) dokazano je da su Zinfandel i Primitivo istog genotipa, tj. genetski sinonimi, a da je Plavac mali posebna sorta. Međutim, stupanj genetske sličnosti između biljega DNA upućuje da su Plavac mali i Zinfandel/Primitivo srodni na razini kakva se nalazi između roditelja i potomaka.Besides its high quality wine, cv. Plavac mali is also famous as a possible synonym for cv. Zinfandel, widely grown in California, and cv. Primitivo, grown in Southern Italy. The supposition that Plavac mali is actually native to Croatia (Dalmatia region) and was introduced to Italy and named as Primitivo, and also introduced to California where it is named as Zinfandel, has been scientifically examined. Based on a comparison of climate requirements for growth and development for each of the above mentioned cultivars, we judged that Plavac mali cannot be of the same genotype as cv. Primitivo or Zinfandel. DNA marker analysis (microsatellites) has proven that Zinfandel and Primitivo share the same genotype, i.e., they are genetically synonyms, but cv. Plavac mali is a distinct variety. However, the degree of genetic similarity among the DNA markers suggests that Plavac mali and Zinfandel/Primitivo probably are related as parent and progeny

Summary from an international cancer seminar focused on human papillomavirus (HPV)-positive oropharynx cancer, convened by scientists at IARC and NCI

Cancer of the oropharynx has attracted considerable attention in recent years given: (1) an increasing incidence in selected populations over the past three decades; (2) the discovery of human papillomavirus (HPV) infection as the driver of the increase, as opposed to the traditional risk factors such as tobacco (smoking and chewing) and alcohol; and (3) the promise of new prevention and treatment strategies. As a result of such developments, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI), convened the fourth Cancer Seminar meeting in November 2018 to focus on this topic. This report summarizes the proceedings: a review of recent science on the descriptive epidemiology, etiology, biology, genetics, early detection, pathology and treatment of HPV-positive oropharyngeal cancer, and the formulation of key research questions to be addressed

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways