Genetic Linkage

Publication Title: 
BMC medical genetics

BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS: We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families.

Author(s): 
Lunetta, Kathryn L.
D'Agostino, Ralph B.
Karasik, David
Benjamin, Emelia J.
Guo, Chao-Yu
Govindaraju, Raju
Kiel, Douglas P.
Kelly-Hayes, Margaret
Massaro, Joseph M.
Pencina, Michael J.
Seshadri, Sudha
Murabito, Joanne M.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

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.

Author(s): 
Puca, A. A.
Daly, M. J.
Brewster, S. J.
Matise, T. C.
Barrett, J.
Shea-Drinkwater, M.
Kang, S.
Joyce, E.
Nicoli, J.
Benson, E.
Kunkel, L. M.
Perls, T.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Recently, chromosome 4q25 was linked to exceptional human longevity, and a haplotype of the positional candidate microsomal transfer protein (MTP) gene was associated to the phenotype in U.S. Caucasians. We investigated whether linkage to 4q25 could be detected in 164 nonagenarian sibships of the Leiden Longevity Study. Additionally, we compared the MTP -493G/T and Q95H allele and haplotype frequencies in the Leiden Longevity Study (379 nonagenarians, 525 of their offspring, and 251 partners of their offspring) and in the Leiden 85-Plus Study (655 octogenarians and 244 young controls).

Author(s): 
Beekman, Marian
Blauw, Gerard Jan
Houwing-Duistermaat, Jeanine J.
Brandt, Bernd W.
Westendorp, Rudi G. J.
Slagboom, P. Eline
Publication Title: 
PloS One

BACKGROUND: Human lifespan is approximately 25% heritable, and genetic factors may be particularly important for achieving exceptional longevity. Accordingly, siblings of centenarians have a dramatically higher probability of reaching extreme old age than the general population. METHODOLOGY/PRINCIPAL FINDINGS: To map the loci conferring a survival advantage, we performed the second genomewide linkage scan on human longevity and the first using a high-density marker panel of single nucleotide polymorphisms.

Author(s): 
Boyden, Steven E.
Kunkel, Louis M.
Publication Title: 
PloS One

BACKGROUND: Although there is abundant evidence that human longevity is heritable, efforts to map loci responsible for variation in human lifespan have had limited success. METHODOLOGY/PRINCIPAL FINDINGS: We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of both familial longevity and individual longevity. This selection identified 325 related "affected individuals", defined as those in the top quartile for both excess longevity (EL?

Author(s): 
Kerber, Richard A.
O'Brien, Elizabeth
Boucher, Kenneth M.
Smith, Ken R.
Cawthon, Richard M.
Publication Title: 
PloS One

BACKGROUND: Although there is abundant evidence that human longevity is heritable, efforts to map loci responsible for variation in human lifespan have had limited success. METHODOLOGY/PRINCIPAL FINDINGS: We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of both familial longevity and individual longevity. This selection identified 325 related "affected individuals", defined as those in the top quartile for both excess longevity (EL?

Author(s): 
Kerber, Richard A.
O'Brien, Elizabeth
Boucher, Kenneth M.
Smith, Ken R.
Cawthon, Richard M.
Publication Title: 
Aging Cell

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project.

Author(s): 
Beekman, Marian
BlanchÈ, HÈlËne
Perola, Markus
Hervonen, Anti
Bezrukov, Vladyslav
Sikora, Ewa
Flachsbart, Friederike
Christiansen, Lene
de Craen, Anton J. M.
Kirkwood, Tom B. L.
Rea, Irene Maeve
Poulain, Michel
Robine, Jean-Marie
Valensin, Silvana
Stazi, Maria Antonietta
Passarino, Giuseppe
Deiana, Luca
Gonos, Efstathios S.
Paternoster, Lavinia
S¯rensen, Thorkild I. A.
Tan, Qihua
Helmer, Quinta
van den Akker, Erik B.
Deelen, Joris
Martella, Francesca
Cordell, Heather J.
Ayers, Kristin L.
Vaupel, James W.
Tˆrnwall, Outi
Johnson, Thomas E.
Schreiber, Stefan
Lathrop, Mark
Skytthe, Axel
Westendorp, Rudi G. J.
Christensen, Kaare
Gampe, Jutta
Nebel, Almut
Houwing-Duistermaat, Jeanine J.
Slagboom, Pieternella Eline
Franceschi, Claudio
GEHA consortium
Publication Title: 
Journal of Human Genetics

Bivariate survival models with discretely distributed frailty based on the major gene concept and applied to the data on related individuals such as twins and sibs can be used to estimate the underlying hazard, the relative risk and the frequency of the longevity allele. To determine the position of the longevity gene, additional genetic markers data are needed. If the action of the longevity allele does not depend on its position in the genome, these two problems can be solved separately using a two-step procedure.

Author(s): 
Begun, Alexander
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

A tandemly repeated DNA hexanucleotide sequence, 5'C-C-C-C-A-A3', that occurs at the termini of extrachromosomal DNA molecules coding for rRNA (rDNA) in Tetrahymena macronuclei was examined to determine whether it is packaged as nucleosomes. This repeated DNA sequence comprises the terminal few hundred base pairs at each end of the linear rDNA molecules.

Author(s): 
Blackburn, E. H.
Chiou, S. S.
Publication Title: 
Genetics

The abundant rDNA minichromosome of Tetrahymena thermophila is generated by a series of developmentally controlled processing steps, termed rDNA maturation, during the formation of the new macronucleus in conjugating cells. rDNA maturation involves excision of a region encoding the single copy rRNA gene (rDNA) from its germline location, rearrangement of the rDNA into a palindromic minichromosome, de novo telomere addition, and amplification to approximately 10(4) copies. The rDNA is maintained at this high level in vegetatively growing cells.

Author(s): 
Kapler, G. M.
Orias, E.
Blackburn, E. H.

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