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. 2001 Aug 28;98(18):10505-8.
doi: 10.1073/pnas.181337598. Epub 2001 Aug 27.

A Genome-Wide Scan for Linkage to Human Exceptional Longevity Identifies a Locus on Chromosome 4

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Free PMC article

A Genome-Wide Scan for Linkage to Human Exceptional Longevity Identifies a Locus on Chromosome 4

A A Puca et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

Substantial evidence supports the familial aggregation of exceptional longevity. The existence of rare families demonstrating clustering for this phenotype suggests that a genetic etiology may be an important component. Previous attempts at localizing loci predisposing for exceptional longevity have been limited to association studies of candidate gene polymorphisms. In this study, a genome-wide scan for such predisposing loci was conducted by using 308 individuals belonging to 137 sibships demonstrating exceptional longevity. By using nonparametric analysis, significant evidence for linkage was noted for chromosome 4 at D4S1564 with a MLS of 3.65 (P = 0.044). The analysis was corroborated by a parametric analysis (P = 0.052). These linkage results indicate the likelihood that there exists a gene, or genes, that exerts a substantial influence on the ability to achieve exceptional old age. Identification of the genes in humans that allow certain individuals to live to extreme old age should lead to insights on cellular pathways that are important to the aging process.

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Figure 1
Figure 1
Multipoint lod scores for the genome-wide scan. Individuals in 137 sibships demonstrating exceptional longevity were genotyped at 400 marker loci throughout the genome. Scores are plotted as a function of specific markers. Chromosome number is designated at the top of each plot. The horizontal threshold lines on each graph represent MLS = 2.0, a score slightly higher than the average maximum score expected by chance once in a genome scan.

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