Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity.

Abstract:

:Hundreds of genes reside in structurally complex, poorly understood regions of the human genome. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity, although genome-wide association studies for obesity have found this locus unremarkable. Using whole-genome sequence analysis, droplet digital PCR and genome mapping, we identified eight common structural haplotypes of the amylase locus that suggest its mutational history. We found that the AMY1 copy number in an individual's genome is generally even (rather than odd) and partially correlates with nearby SNPs, which do not associate with body mass index (BMI). We measured amylase gene copy number in 1,000 obese or lean Estonians and in 2 other cohorts totaling ∼3,500 individuals. We had 99% power to detect the lower bound of the reported effects on BMI, yet found no association.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Usher CL,Handsaker RE,Esko T,Tuke MA,Weedon MN,Hastie AR,Cao H,Moon JE,Kashin S,Fuchsberger C,Metspalu A,Pato CN,Pato MT,McCarthy MI,Boehnke M,Altshuler DM,Frayling TM,Hirschhorn JN,McCarroll SA

doi

10.1038/ng.3340

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

921-5

issue

8

eissn

1061-4036

issn

1546-1718

pii

ng.3340

journal_volume

47

pub_type

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