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Methods Mol Biol. 2019;1890:251-257. doi: 10.1007/978-1-4939-8900-3_21.

Analysis of FOXO3 Gene Polymorphisms Associated with Human Longevity.

Author information

1
Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Honolulu, HI, USA.
2
John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
3
Institute for Biogenesis Research, University of Hawaii, Honolulu, HI, USA.
4
Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Honolulu, HI, USA. willcoxbj@gmail.com.
5
Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. willcoxbj@gmail.com.

Abstract

Next-generation DNA sequencing has ushered in a new era of genotype-phenotype comparisons that have the potential to elucidate the genetic nature of complex traits. Since such methods rely on short sequence reads and since the human genome is composed largely of repetitive DNA elements larger than these read lengths many results cannot be mapped and are discarded, thus eliminating a large portion of the genome from analysis. Discerning associations in complex traits, such as longevity, will require either longer read lengths or methods to address these sequence complexities. Whole genome analysis, such as Genome Wide Association Studies (GWAS), also suffers from the repetitive nature of the human genome, as there exist many gaps in the availability of useable genetic markers, often in interesting regulatory regions. Methods are described here whereby some of these problems have been addressed by targeted DNA sequencing, full exploitation of available public databases, and a careful evaluation of genomic features where we use the FOXO3 gene as an example to identify functional variations and how they may relate to longevity.

KEYWORDS:

Genome complexity; Long-range DNA sequencing; Long-range PCR; Repetitive DNA

PMID:
30414160
DOI:
10.1007/978-1-4939-8900-3_21
[Indexed for MEDLINE]

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