Pattern of nucleotide substitutions.

<p>Novel coding single-nucleotide variants were divided and counted according to substitution class in the six melanoma cell lines.</p

Melanoma-related genes mutated in the six melanoma cell lines.

*<p>truncating mutation (stop codon);</p>§<p>double-mutated in the same sample;</p>Δ<p>homozygous mutation (AF = 1);</p>&<p>mutation of one allele together with one-copy deletion of the other one. Genes mutated in at least two samples are underlined. NS/S represents the non-synonymous to synonymous mutation count calculated for the whole molecular pathway or function class.</p

Copper Age sheep nucleotide polymorphisms relative to <i>Ovis aries</i> reference sequence (NC001941).

<p>⁽⁴⁵⁴⁾: nucleotide polymorphism analyzed by 454 technology; ^(S): nucleotide polymorphism variations analyzed by Sanger technology; ^×: ambiguous nucleotide position.</p

Comprehensive Genomic Characterization of Cutaneous Malignant Melanoma Cell Lines Derived from Metastatic Lesions by Whole-Exome Sequencing and SNP Array Profiling

<div><p>Cutaneous malignant melanoma is the most fatal skin cancer and although improved comprehension of its pathogenic pathways allowed to realize some effective molecular targeted therapies, novel targets and drugs are still needed. Aiming to add genetic information potentially useful for novel targets discovery, we performed an extensive genomic characterization by whole-exome sequencing and SNP array profiling of six cutaneous melanoma cell lines derived from metastatic patients. We obtained a total of 3,325 novel coding single nucleotide variants, including 2,172 non-synonymous variants. We catalogued the coding mutations according to Sanger COSMIC database and to a manually curated list including genes involved in melanoma pathways identified by mining recent literature. Besides confirming the presence of known melanoma driver mutations (<i>BRAF^V600E, NRAS^Q61R</i>), we identified novel mutated genes involved in signalling pathways crucial for melanoma pathogenesis and already addressed by current targeted therapies (such as MAPK and glutamate pathways). We also identified mutations in four genes (<i>MUC19</i>, <i>PAICS</i>, <i>RBMXL1</i>, <i>KIF23</i>) never reported in melanoma, which might deserve further investigations. All data are available to the entire research community in our Melanoma Exome Database (at <a href="https://155.253.6.64/MExDB/" target="_blank">https://155.253.6.64/MExDB/</a>). In summary, these cell lines are valuable biological tools to improve the genetic comprehension of this complex cancer disease and to study functional relevance of individual mutational events, and these findings could provide insights potentially useful for identification of novel therapeutic targets for cutaneous malignant melanoma.</p></div

Recurrent de novo mutated genes.

<p>Literature is indicated by PubMed ID code (PMID). References in italics concern other members of the same gene family involved in cancer and here reported to support a potential interest for the listed mutated genes.</p><p>Abbreviations: NS, non-synonymous; GO, Gene Ontology; ALL, acute lymphoblastic leukemia; NSCLC, non-small cell lung cancer.</p

Nucleotide misincorporation rate (<i>m</i>) in Copper Age sheep, Copper Age human (Ötzi) and modern human mtDNA.

<p>The plot comprises a box and whiskers. A line is drawn across the box to represent the median; the bottom of the box is the first quartile (Q1) and the top is the third quartile (Q3). The lower whisker extends to the lowest value within the lower limit, while the upper whisker extends to the highest value within the upper limit. The limits are defined by: Q1+1.5 (Q3-Q1) (lower limit) and Q3+1.5 (Q3-Q1) (upper limit). The asterisk represent the outlier, a value beyond the whiskers.</p

Single nucleotide variants (SNVs) summary.

<p>Abbreviations: SNVs, single nucleotide variants; HQ-SNVs, high-quality single nucleotide variants.</p

Median-joining phylogenetic network of modern sheep based on 336 sequences and rooted with <i>Ovis vignei</i> (H_2).

<p>Each cluster symbolized by a circle refers to a haplogroup. Line connecting each circle represents phylogenetic branches. Numbers along each branch are transitions and refer to nucleotide positions variants relative to <i>Ovis aries</i> reference sequence (NC_001941). * paraphyletic group.</p

Confirmed COSMIC mutations and deletions.

<p>In the column “mutated”, we listed COSMIC genes for which we found mutation on the same genomic position as reported in COSMIC database (v58). In the column “deleted”, we listed COSMIC genes for which we confirmed deletion spanning the entire gene locus. Genes recurrent in at least two samples are underlined.</p>*<p>truncating mutation (stop codon);</p>Δ<p>homozygous mutation (AF = 1);</p>#<p>homozygous deletion (two-copy loss).</p

Positioning the Red Deer (<i>Cervus elaphus</i>) Hunted by the Tyrolean Iceman into a Mitochondrial DNA Phylogeny

<div><p>In the last years several phylogeographic studies of both extant and extinct red deer populations have been conducted. Three distinct mitochondrial lineages (western, eastern and North-African/Sardinian) have been identified reflecting different glacial refugia and postglacial recolonisation processes. However, little is known about the genetics of the Alpine populations and no mitochondrial DNA sequences from Alpine archaeological specimens are available. Here we provide the first mitochondrial sequences of an Alpine Copper Age <i>Cervus elaphus</i>. DNA was extracted from hair shafts which were part of the remains of the clothes of the glacier mummy known as the Tyrolean Iceman or Ötzi (5,350–5,100 years before present). A 2,297 base pairs long fragment was sequenced using a mixed sequencing procedure based on PCR amplifications and 454 sequencing of pooled amplification products. We analyzed the phylogenetic relationships of the Alpine Copper Age red deer's haplotype with haplotypes of modern and ancient European red deer. The phylogenetic analyses showed that the haplotype of the Alpine Copper Age red deer falls within the western European mitochondrial lineage in contrast with the current populations from the Italian Alps belonging to the eastern lineage. We also discussed the phylogenetic relationships of the Alpine Copper Age red deer with the populations from Mesola Wood (northern Italy) and Sardinia.</p></div