title: A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4.
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.
authors.affiliation: Howard Hughes Medical Institute, Genetics Division, Children's Hospital, and Harvard Medical School, Boston, MA 02215, USA. apuca@rascal.med.harvard.edu
authors.forename: A A
authors.initials: AA
authors.lastname: Puca
authors.forename: M J
authors.initials: MJ
authors.lastname: Daly
authors.forename: S J
authors.initials: SJ
authors.lastname: Brewster
authors.forename: T C
authors.initials: TC
authors.lastname: Matise
authors.forename: J
authors.initials: J
authors.lastname: Barrett
authors.forename: M
authors.initials: M
authors.lastname: Shea-Drinkwater
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.forename: E
authors.initials: E
authors.lastname: Joyce
authors.forename: J
authors.initials: J
authors.lastname: Nicoli
authors.forename: E
authors.initials: E
authors.lastname: Benson
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
authors.forename: T
authors.initials: T
authors.lastname: Perls
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008136:Longevity / Q000235:genetics*; D008297:Male; D009679:Nuclear Family