Dataset Information

Gene Expression Differences Between Offspring of Long-Lived Individuals and Controls in Candidate Longevity Regions: Evidence for PAPSS2 as a Longevity Gene.

ABSTRACT: Although there is compelling evidence for a genetic contribution to longevity, identification of specific genes that robustly associate with longevity has been a challenge. In order to identify longevity-enhancing genes, we measured differential gene expression between offspring of long-lived Amish (older than 90 years; cases, n = 128) and spouses of these offspring (controls, n = 121) and correlated differentially expressed transcripts with locations of longevity-associated variants detected in a prior genome-wide association study (GWAS) of survival to age 90. Expression of one of these transcripts, 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2), was significantly higher in offspring versus controls (4×10(-4)) and this association was replicated using quantitative real-time polymerase chain reaction. PAPSS2, a sulfation enzyme located on chromosome 10, is ~80kb upstream of the PAPSS2 transcription start site. We found evidence of cis-expression for the originally reported GWAS SNP and PAPSS2 Monogenic conditions linked to PAPSS2 include andrenocortical androgen excess resulting in premature pubarche and skeletal dysplasias, both of which have premature aging features. In summary, these findings provide novel evidence for PAPSS2 as a longevity locus and illustrate the value of harnessing multiple "-omic" approaches to identify longevity candidates.

SUBMITTER: Yerges-Armstrong LM

PROVIDER: S-EPMC5018562 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Gene Expression Differences Between Offspring of Long-Lived Individuals and Controls in Candidate Longevity Regions: Evidence for PAPSS2 as a Longevity Gene.

Yerges-Armstrong Laura M LM Chai Sumbul S O'Connell Jeffery R JR Curran Joanne E JE Blangero John J Mitchell Braxton D BD Shuldiner Alan R AR Damcott Coleen M CM

The journals of gerontology. Series A, Biological sciences and medical sciences 20160219 10

Although there is compelling evidence for a genetic contribution to longevity, identification of specific genes that robustly associate with longevity has been a challenge. In order to identify longevity-enhancing genes, we measured differential gene expression between offspring of long-lived Amish (older than 90 years; cases, n = 128) and spouses of these offspring (controls, n = 121) and correlated differentially expressed transcripts with locations of longevity-associated variants detected in ...[more]

PMID: 26896383

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Project description:The candidate division TM7 is ubiquitous and yet uncultured phylum of the Bacteria that encompasses a commonly environmental associated clade, TM7-1, and a "host-associated" clade, TM7-3. However, as members of the TM7 phylum have not been cultured, little is known about what differs between these two clades. We hypothesized that these clades would have different environmental niches. To test this, we used a large-scale global soil dataset, encompassing 223 soil samples, their environmental parameters and associated bacterial 16S rRNA gene sequence data. We correlated chemical, physical and biological parameters of each soil with the relative abundance of the two major classes of the phylum to deduce factors that influence the groups' seemingly ubiquitous nature. The two classes of the phylum (TM7-1 and TM7-3) were indeed distinct from each other in their habitat requirements. A key determinant of each class' prevalence appears to be the pH of the soil. The class TM7-1 displays a facultative anaerobic nature with correlations to more acidic soils with total iron, silicon, titanium and copper indicating a potential for siderophore production. However, the TM7-3 class shows a more classical oligotrophic, heterotroph nature with a preference for more alkaline soils, and a probable pathogenic role with correlations to extractable iron, sodium and phosphate. In addition, the TM7-3 was abundant in diesel contaminated soils highlighting a resilient nature along with a possible carbon source. In addition to this both classes had unique co-occurrence relationships with other bacterial phyla. In particular, both groups had opposing correlations to the Gemmatimonadetes phylum, with the TM7-3 class seemingly being outcompeted by this phylum to result in a negative correlation. These ecological controls allow the characteristics of a TM7 phylum preferred niche to be defined and give insight into possible avenues for cultivation of this previously uncultured group.

Dataset Information

Gene Expression Differences Between Offspring of Long-Lived Individuals and Controls in Candidate Longevity Regions: Evidence for PAPSS2 as a Longevity Gene.

Publications

Gene Expression Differences Between Offspring of Long-Lived Individuals and Controls in Candidate Longevity Regions: Evidence for PAPSS2 as a Longevity Gene.

Similar Datasets

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