Exome sequencing of three cases of familial exceptional longevity
Version of Record online: 12 AUG 2014
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 6, pages 1087–1090, December 2014
How to Cite
Cash, T. P., Pita, G., Domínguez, O., Alonso, M. R., Moreno, L. T., Borrás, C., Rodríguez-Mañas, L., Santiago, C., Garatachea, N., Lucia, A., Avellana, J. A., Viña, J., González-Neira, A. and Serrano, M. (2014), Exome sequencing of three cases of familial exceptional longevity. Aging Cell, 13: 1087–1090. doi: 10.1111/acel.12261
- Issue online: 24 NOV 2014
- Version of Record online: 12 AUG 2014
- Manuscript Accepted: 7 JUL 2014
- European Union. Grant Number: FP7 RISK-IR
- Regional Government of Madrid (ReCaRe)
- Botin Foundation
- Ramon Areces Foundation
- AXA Foundation
- RETICEF (Red Española en Envejecimiento y Fragilidad)
- apolipoprotein B;
- exome sequencing;
- rare variants
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.