Ten Rare, Non-synonymous Variants Shared by Individuals IV:11 and IV:18 of Family PARK_0005.

<p>The rare variants common to the two affected individuals were genotyped in 975 cases and 1014 controls. Penetrance with regard to the PD phenotype was assessed in 6 family members belonging to the same generation as the affected individuals. EA = European American.</p

Qualitative multifactorial interaction network of <i>PLXNA4</i> and genetic factors with known and hypothetical relevance to PD.

<p>Edges obtained from CIDeR are highlighted in blue, PD-specific pathways from KEGG are given in green, red edges denote annotations from OMIM and edges extracted from literature, protein-protein interaction databases or high-confidence predictions are colored black. Undirected protein-protein interactions hold circular ends, directed molecular relations are marked by arcs, whereas general regulations have arrows with no filling, activations have filled arrows and inhibitions have blunted end. Dashed lines indicate indirect effects.</p

Pedigree and Linkage Analysis.

<p>(A) Pedigree of family used for exome sequencing. Open symbols indicate unaffected family members, affected individuals are denoted by closed symbols. An arrow denotes the individuals whose exomes were sequenced. Sex was obscured and birth order was altered to protect privacy. A diagonal line indicates a deceased individual. (B) 25 genomic regions on 12 chromosomes with logarithm of the odds (LOD) score≥0.5 were identified by linkage analysis. Green boxes represent genomic regions with LOD≥0.5, yellow stars represent the location of the four candidate genes remaining after frequency assessment (<i>GOLGA4</i>-chr3, <i>PLXNA4</i>-chr7, <i>OGN</i>-chr9, <i>CPNE1</i>-chr20). <i>PLXNA4</i> on chromosome 7 represents the only of the four genes overlapping a genomic region with LOD≥0.5.</p

Assessment of cell viability and subcellular protein localization in fibroblasts.

<p>(A) The presence of <i>PLXNA4</i> p.Ser657Asn do not affect cell viability as assay by live-dead staining and FACS. (B) Immunohistochemistry shows similar subcellular localization of <i>PLXNA4</i> (anti-PLXNA4, Sigma, 1∶500) in fibroblasts with and without the p.Ser657Asn amino acid substitution (scale bar = 50 µm).</p