6533b7dcfe1ef96bd1272133

RESEARCH PRODUCT

Exome sequencing of three cases of familial exceptional longevity

Catalina SantiagoJuan A. AvellanaAnna González-neiraAlejandro LuciaOrlando DomínguezNuria GaratacheaManuel SerranoJose ViñaTimothy P. CashLeticia T. MorenoGuillermo PitaConsuelo BorrasLeocadio Rodríguez-mañasMaría R Alonso

subject

Exome sequencingCienciaMaleAgingCandidate genemedia_common.quotation_subjectLongevityEnvejecimientoBiologyGene FrequencyCentenariansGenetic variationapolipoprotein BHumansExomeAllele frequencyGeneExomeExome sequencingmedia_commonGeneticsShort TakesAged 80 and overFamily HealthLongevityrare variantsGenetic VariationRare variantsCell BiologyGenéticaMinor allele frequencyApolipoprotein B-100FemalecentenariansApolipoprotein Bexome sequencing

description

Exceptional longevity (EL) is a rare phenotype that can cluster in families, and co-segregation of genetic variation in these families may point to candidate genes that could contribute to extended lifespan. In this study, for the first time, we have sequenced a total of seven exomes from exceptionally long-lived siblings (probands ≥ 103 years and at least one sibling ≥ 97 years) that come from three separate families. We have focused on rare functional variants (RFVs) which have ≤ 1% minor allele frequency according to databases and that are likely to alter gene product function. Based on this, we have identified one candidate longevity gene carrying RFVs in all three families, APOB. Interestingly, APOB is a component of lipoprotein particles together with APOE, and variants in the genes encoding these two proteins have been previously associated with human longevity. Analysis of nonfamilial EL cases showed a trend, without reaching statistical significance, toward enrichment of APOB RFVs. We have also identified candidate longevity genes shared between two families (5-13) or within individual families (66-156 genes). Some of these genes have been previously linked to longevity in model organisms, such as PPARGC1A, NRG1, RAD52, RAD51, NCOR1, and ADCY5 genes. This work provides an initial catalog of genes that could contribute to exceptional familial longevity.

10.1111/acel.12261http://europepmc.org/articles/PMC4326919