Figure 1.
Leu cocyte telomere lengths (TLs) do not cosegregate with heterozygous PARN (polyadenylation-specific ribonuclease deadenylation nuclease) mutations in a familial pulmonary fibrosis kindred. (A) Abridged pedigree of one kindred with familial pulmonary fibrosis and the cosegregating PARN c.529C>T (Gln177*) mutation. Individuals with pulmonary fibrosis are indicated by black filled symbols; individuals with blood leucocyte TLs <1st percentile, <5th percentile and <10th percentile are indicated by red, green and blue symbols, respectively. The arrow denotes the proband. Numbers in parentheses indicate individuals for whom no DNA sample is available. The presence or absence of the heterozygous PARN mutation is indicated by ‘Mut’ or ‘WT’, respectively. The age at the time of blood draw or death is indicated to the upper right of each symbol. (B) Genomic DNA telomere measured using a multiplexed quantitative PCR assay and expressed as age-adjusted (observed minus expected) TLs.3 (C) Genetic linkage analysis of kindred shown in A. Multipoint model-based analysis of genomic linkage identifies a peak on chromosome 16 with a maximal LOD score of 2.6 (p value ≤2.5×10−3) that does not encompass the PARN gene (location indicated by the arrow). All affected individuals share a segment of 37.1 Mb identical-by-descent bounded by markers rs229007 and rs17281761.