Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma

Although CDKN2A is the most frequent high-risk melanoma susceptibility gene, the underlying genetic factors for most melanoma-prone families remain unknown. Using whole-exome sequencing, we identified a rare variant that arose as a founder mutation in the telomere shelterin gene POT1 (chromosome 7, g.124493086C>T; p.Ser270Asn) in five unrelated melanoma-prone families from Romagna, Italy. Carriers of this variant had increased telomere lengths and numbers of fragile telomeres, suggesting that this variant perturbs telomere maintenance. Two additional rare POT1 variants were identified in all cases sequenced in two separate Italian families, one variant per family, yielding a frequency for POT1 variants comparable to that for CDKN2A mutations in this population. These variants were not found in public databases or in 2,038 genotyped Italian controls. We also identified two rare recurrent POT1 variants in US and French familial melanoma cases. Our findings suggest that POT1 is a major susceptibility gene for familial melanoma in several populations

Ploidy manipulation and citrus breeding, genetics and genomics

Polyploidy appears to have played a limited role in citrus germplasm evolution. However, today, ploidy manipulation is an important component of citrus breeding strategies. For varieties, the main objective is to develop triploid seedless varieties. For rootstock, the aim is to cumulate interesting traits in tetraploid hybrids and to improve adaptation to biotic and abiotic stresses. In this chapter we make a review of the recent knowledge acquired on the natural mechanisms of citrus polyploidization, and teraploid meiosis. Chromosome doubling of nucellar cells is frequent in apomictic citrus and results in tetraploid seedling production. Unreduced gametes are also frequently produced, mainly by second division restitution for ovules. First division restitution was described for pollen as well as alternative mechanisms for both ovules and pollen. Tetraploid plants display tetrasomic to disomic segregations in relation with their genome structure (autoteraploid versus allotetraploid) and the divergence of the parental species. The implications of the origin of diploid gametes, on the genetic diversity of polyploid progenies, are discussed. The biotechnological tools (haplo-methods, chromosome doubling by chemichal treatments, somatic hybridization and cytogenetic/molecular tools for polyploid genome studies) to optimize ploidy manipulation are presented. The interest of haploids and polyploid genotypes for basic genetic and genomic studies is discussed. The following research area are reviewed: haploids and doubled haploid for genome sequencing and haplotyping, centromere mapping from unreduced gametes, marker-trait association study in polyploids, phenome and gene expression in polyploids with a special focus on polyploidy and adaptation. Finally, we give an overview of the recent advances of concrete polyploid citrus breeding programs in China, Florida and the Mediterranean Basin