Mapping of a major locus that determines telomere length in humans

Mariuca Vasa-Nicotera; Scott Brouilette; Massimo Mangino; John R Thompson; Peter Braund; Jenny-Rebecca Clemitson; Andrea Mason; Clare L Bodycote; Stuart M Raleigh; Edward Louis; Nilesh J Samani

doi:10.1086/426734

Mapping of a major locus that determines telomere length in humans

Mariuca Vasa-Nicotera, Scott Brouilette, Massimo Mangino, John R Thompson, Peter Braund, Jenny-Rebecca Clemitson, Andrea Mason, Clare L Bodycote, Stuart M Raleigh, Edward Louis, Nilesh J Samani

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

223 Citations (Scopus)

Abstract

Telomere length is a crucial factor for both normal chromosomal function and senescence. Mean telomere length in humans shows considerable interindividual variation and strong genetic determination. To see if a locus (or loci) affecting telomere length in humans could be mapped, we performed a quantitative-trait linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths, measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs. Heritability of mean (+/-SE) TRF was 81.9%+/-11.8%. There was significant linkage (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained 49% of the overall variability in mean TRF length. We present preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11. In conclusion, we report mapping of the first locus that determines mean telomere length in humans. Identification of the gene involved and elucidation of its mechanism of action could have important implications for our understanding of chromosomal assembly, telomere biology, and susceptibility to age-related diseases.

Original language	English
Pages (from-to)	147-151
Number of pages	5
Journal	American Journal of Human Genetics
Volume	76
Issue number	1
DOIs	https://doi.org/10.1086/426734
Publication status	Published - Jan 2005

Keywords

Adolescent
Adult
Aged
Chromosome Mapping
Chromosomes, Human, Pair 12
Coronary Disease
DEAD-box RNA Helicases
DNA Helicases
Female
Humans
Leukocytes
Lod Score
Male
Microsatellite Repeats
Middle Aged
Quantitative Trait Loci
Telomere
Ultrasonography
Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/426734

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title = "Mapping of a major locus that determines telomere length in humans",

abstract = "Telomere length is a crucial factor for both normal chromosomal function and senescence. Mean telomere length in humans shows considerable interindividual variation and strong genetic determination. To see if a locus (or loci) affecting telomere length in humans could be mapped, we performed a quantitative-trait linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths, measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs. Heritability of mean (+/-SE) TRF was 81.9%+/-11.8%. There was significant linkage (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained 49% of the overall variability in mean TRF length. We present preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11. In conclusion, we report mapping of the first locus that determines mean telomere length in humans. Identification of the gene involved and elucidation of its mechanism of action could have important implications for our understanding of chromosomal assembly, telomere biology, and susceptibility to age-related diseases.",

keywords = "Adolescent, Adult, Aged, Chromosome Mapping, Chromosomes, Human, Pair 12, Coronary Disease, DEAD-box RNA Helicases, DNA Helicases, Female, Humans, Leukocytes, Lod Score, Male, Microsatellite Repeats, Middle Aged, Quantitative Trait Loci, Telomere, Ultrasonography, Journal Article, Research Support, Non-U.S. Gov't",

author = "Mariuca Vasa-Nicotera and Scott Brouilette and Massimo Mangino and Thompson, {John R} and Peter Braund and Jenny-Rebecca Clemitson and Andrea Mason and Bodycote, {Clare L} and Raleigh, {Stuart M} and Edward Louis and Samani, {Nilesh J}",

year = "2005",

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doi = "10.1086/426734",

language = "English",

volume = "76",

pages = "147--151",

journal = "American Journal of Human Genetics",

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T1 - Mapping of a major locus that determines telomere length in humans

AU - Vasa-Nicotera, Mariuca

AU - Brouilette, Scott

AU - Mangino, Massimo

AU - Thompson, John R

AU - Braund, Peter

AU - Clemitson, Jenny-Rebecca

AU - Mason, Andrea

AU - Bodycote, Clare L

AU - Raleigh, Stuart M

AU - Louis, Edward

AU - Samani, Nilesh J

PY - 2005/1

Y1 - 2005/1

N2 - Telomere length is a crucial factor for both normal chromosomal function and senescence. Mean telomere length in humans shows considerable interindividual variation and strong genetic determination. To see if a locus (or loci) affecting telomere length in humans could be mapped, we performed a quantitative-trait linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths, measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs. Heritability of mean (+/-SE) TRF was 81.9%+/-11.8%. There was significant linkage (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained 49% of the overall variability in mean TRF length. We present preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11. In conclusion, we report mapping of the first locus that determines mean telomere length in humans. Identification of the gene involved and elucidation of its mechanism of action could have important implications for our understanding of chromosomal assembly, telomere biology, and susceptibility to age-related diseases.

AB - Telomere length is a crucial factor for both normal chromosomal function and senescence. Mean telomere length in humans shows considerable interindividual variation and strong genetic determination. To see if a locus (or loci) affecting telomere length in humans could be mapped, we performed a quantitative-trait linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths, measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs. Heritability of mean (+/-SE) TRF was 81.9%+/-11.8%. There was significant linkage (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained 49% of the overall variability in mean TRF length. We present preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11. In conclusion, we report mapping of the first locus that determines mean telomere length in humans. Identification of the gene involved and elucidation of its mechanism of action could have important implications for our understanding of chromosomal assembly, telomere biology, and susceptibility to age-related diseases.

KW - Adolescent

KW - Adult

KW - Aged

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 12

KW - Coronary Disease

KW - DEAD-box RNA Helicases

KW - DNA Helicases

KW - Female

KW - Humans

KW - Leukocytes

KW - Lod Score

KW - Male

KW - Microsatellite Repeats

KW - Middle Aged

KW - Quantitative Trait Loci

KW - Telomere

KW - Ultrasonography

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1086/426734

M3 - Article

C2 - 15520935

SN - 0002-9297

VL - 76

SP - 147

EP - 151

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 1

ER -

Mapping of a major locus that determines telomere length in humans

Abstract

Keywords

UN SDGs

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