New Insight into the History of Domesticated Apple: Secondary Contribution of the European Wild Apple to the Genome of Cultivated Varieties

The apple is the most common and culturally important fruit crop of temperate areas. The elucidation of its origin and domestication history is therefore of great interest. The wild Central Asian species Malus sieversii has previously been identified as the main contributor to the genome of the cultivated apple (Malus domestica), on the basis of morphological, molecular, and historical evidence. The possible contribution of other wild species present along the Silk Route running from Asia to Western Europe remains a matter of debate, particularly with respect to the contribution of the European wild apple. We used microsatellite markers and an unprecedented large sampling of five Malus species throughout Eurasia (839 accessions from China to Spain) to show that multiple species have contributed to the genetic makeup of domesticated apples. The wild European crabapple M. sylvestris, in particular, was a major secondary contributor. Bidirectional gene flow between the domesticated apple and the European crabapple resulted in the current M. domestica being genetically more closely related to this species than to its Central Asian progenitor, M. sieversii. We found no evidence of a domestication bottleneck or clonal population structure in apples, despite the use of vegetative propagation by grafting. We show that the evolution of domesticated apples occurred over a long time period and involved more than one wild species. Our results support the view that self-incompatibility, a long lifespan, and cultural practices such as selection from open-pollinated seeds have facilitated introgression from wild relatives and the maintenance of genetic variation during domestication. This combination of processes may account for the diversification of several long-lived perennial crops, yielding domestication patterns different from those observed for annual species

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Vh8 locus of a new gene-for-gene interaction between Venturia inaequalis and the wild applie Malus sieversii is closely linked to the Vh2 locus in Malus pumila R12740-7A

The wild apple (Malus sieversii) is a large-fruited species from Central Asia, which is used as a source of scab resistance in cultivar breeding. Phytopathological tests with races of Venturia inaequalis were performed to differentiate scab-resistance genes in Malus as well as an avirulence gene in the pathogen. A novel gene-for-gene interaction between V. inaequalis and Malus was identified. The locus of the scab-resistance gene Vh8 is linked with, or possibly allelic to, that of the Vh2 gene in Malus pumila Russian apple R12740-7A, at the lower end of linkage group 2 of Malus. Race 8 isolate NZ188B.2 is compatible with Vh8, suggesting the loss or modification of the complementary AvrVh8 gene, while isolate 1639 overcomes both Vh2 and Vh8, but is incompatible with at least one other gene not detected by any of the other race isolates tested. Our research is the first to differentiate scab-resistance genes in a putative gene cluster in apple with the aid of races of V. inaequalis

A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease

International audiencePeople with late-stage Parkinson’s disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD

The role of Schmidt 'Antonovka' in apple scab resistance breeding

'Antonovka' has long been recognised as a major source of scab (Venturia inaequalis) resistance useful for apple breeding worldwide. Both major gene resistances in the form of the Rvi10 and Rvi17 and quantitative resistance, collectively identified as VA, have been identified in different accessions of 'Antonovka'. Most of the 'Antonovka' scab resistance used in apple-breeding programmes around the world can be traced back to Schmidt 'Antonovka' and predominantly its B VIII progenies 33,25 (PI 172623), 34,6 (PI 172633), 33,8 (PI 172612) and 34,5 (PI 172632). Using genetic profile reconstruction, we have identified "common 'Antonovka' " as the progenitor of the B VIII family, which is consistent with it having been a commercial cultivar in Poland and the single source of scab resistance used by Dr. Martin Schmidt. The major 'Antonovka' scab resistance genes mapped to date are located either very close to Rvi6, or about 20-25 cM above it, but their identities need further elucidation. The presence of the 139 bp allele of the CH-Vf1 microsatellite marker known to be associated with Rvi17 (Va1) in most of the 'Antonovka' germplasm used in breeding suggests that it plays a central role in the resistance. The nature and the genetic relationships of the scab resistance in these accessions as well as a number of apple cultivars derived from 'Antonovka', such as, 'Freedom', 'Burgundy' and 'Angold', are discussed. The parentage of 'Reglindis' is unclear, but the cultivar commercialised as 'Reglindis' was confirmed to be an Rvi6 cultivar

Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

IF 7.191 (2017)International audienceBACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI <18.5). Interaction tests were performed between BMI effect and sex, age and the addition of antiangiogenics to chemotherapy.RESULTS:The rate of BMI ≥25 patients was 41.5%, ranging from 37.6% (1991-1999 period) to 41.5% (2000-2006 period) and 44.8% (2007-2013 period). Comparison of overweight patients versus normal BMI range patients revealed a significant improvement of median overall survival (OS) (18.5 versus 16.3 months, HR = 0.88 [0.80-0.98] p = 0.02) and objective response rate (ORR) (42% versus 36% OR = 1.23 [1.01-1.50] p = 0.04) but a comparable median progression-free survival (PFS) (7.8 versus 7.2 months, HR = 0.96 [0.87-1.05] p = 0.35). Subgroup analyses revealed that overweight was significantly associated with better OS in men. OS and PFS were significantly shorter in thin patients.CONCLUSION:Overweight patients had a prolonged OS compared with normal weight patients with mCRC. The association of overweight with better OS was only observed in men. The pejorative prognosis of BMI <18.5 was confirmed.Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserve

Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats

Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, >99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysi