Sanger sequencing trace and amino acid alignment showing the truncated BAP1 protein.

<p>(A) The left panel shows the wild type chromatogram while the right panel shows that of the <i>BAP1</i> splice mutation. (B) Wild type nucleotide and amino acid sequences are shown in the upper panel while the lower panel shows part of the truncated BAP1 protein resulting from the loss of exon 8.</p

Co-segregation analysis of a <i>BAP1</i> splice mutation in a Danish family.

<p>In the pedigree individuals that have uveal melanoma (UMM) are represented by black circles (female) or boxes (male) and individuals with cutaneous melanoma (CMM) are indicated by grey circles or boxes. The age of diagnosis of each melanoma is indicated in brackets. A line through a symbol indicates that the person is now deceased. If a person carries the <i>BAP1</i> splice mutation it is indicated by an ‘M’ and if they are wild type for this variant it is indicated with a ‘WT’. Where the mutation status is indicated in brackets, the person is a presumed obligate carrier, ‘(M)’. Other cancer types are also indicated in the pedigree with the age of diagnosis in brackets. Asterisks indicate the two individuals that were exome sequenced. Unaffected siblings are represented by diamonds, with the number in the centre indicating the number of people.</p

RT-PCR showing the aberrantly spliced <i>BAP1</i> transcript.

<p>From the left, the first lane shows a size marker, the next two lanes show wild type <i>BAP1</i> RT-PCR products, and the last two lanes show the aberrantly spliced product resulting from the c.581-2A>G mutation.</p

Clinical phenotypes of current and published UMM cases or their families with <i>BAP1</i> mutations.

<p>na is not available; a has been observed for 41 years without metastatic disease; b has been observed for 16 years without metastatic disease; c has been observed for 1, 4 and 8 years without metastatic disease; d has no information regarding the 4 other UMM cases;</p>*<p>refers to UMM case with unknown age of onset;</p>∧<p>refers to values from columns 1–3;</p>∼<p>refers to values from columns 4–9;</p>§<p>refers to values from columns 1–9.</p

Case-control analysis on non-synonymous <i>PALB2</i> variants.

<p>Case-control analysis on non-synonymous <i>PALB2</i> variants.</p

Co-segregation analysis of <i>PALB2</i> variants in two high-risk CMM families.

<p>Individuals that have melanoma (MM) are represented by black circles (female) and black boxes (male). The age of diagnosis of each cancer is indicated in brackets. A line through a symbol indicates that the person is deceased. Individuals carrying a <i>PALB2</i> mutation are indicated by an ‘M’, while those wild-type for the variant are indicated by ‘WT’. Other cancer types are also indicated on the pedigree. Unaffected siblings are represented by a diamond with the number indicating the number of siblings. The arrow indicates the proband in each family.</p

<i>PALB2</i> variants detected through Sanger sequencing and exome sequencing.

<p>*European American population.</p><p>na is not available.</p

Minor allele frequency (MAF) and odds ratio (OR) of <i>MC1R</i> variants in melanoma cases/families compared to the Danish population.

<p>Minor allele frequency (MAF) and odds ratio (OR) of <i>MC1R</i> variants in melanoma cases/families compared to the Danish population.</p

Characteristics of the 13 individuals/families with identified <i>CDKN2A</i> mutations.

<p>SCC: squamous cell carcinoma</p><p>CLL: chronic lymphocytic leukemia</p><p>RCC: renal cell carcinoma</p><p>Characteristics of the 13 individuals/families with identified <i>CDKN2A</i> mutations.</p

Minor allele frequency (MAF) and odds ratio (OR) of <i>MC1R</i> variants in melanoma cases/families compared to the Danish population.

<p>Minor allele frequency (MAF) and odds ratio (OR) of <i>MC1R</i> variants in melanoma cases/families compared to the Danish population.</p