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Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes

The human salivary amylase genes display extensive copy number variation (CNV), and recent work has implicated this variation in adaptation to starch-rich diets, and in association with body mass index. In this work, we use paralogue ratio tests, microsatellite analysis, read depth and fibre-FISH to...

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Autores principales: Carpenter, Danielle, Dhar, Sugandha, Mitchell, Laura M., Fu, Beiyuan, Tyson, Jess, Shwan, Nzar A.A., Yang, Fengtang, Thomas, Mark G., Armour, John A.L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498156/
https://www.ncbi.nlm.nih.gov/pubmed/25788522
http://dx.doi.org/10.1093/hmg/ddv098
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author Carpenter, Danielle
Dhar, Sugandha
Mitchell, Laura M.
Fu, Beiyuan
Tyson, Jess
Shwan, Nzar A.A.
Yang, Fengtang
Thomas, Mark G.
Armour, John A.L.
author_facet Carpenter, Danielle
Dhar, Sugandha
Mitchell, Laura M.
Fu, Beiyuan
Tyson, Jess
Shwan, Nzar A.A.
Yang, Fengtang
Thomas, Mark G.
Armour, John A.L.
author_sort Carpenter, Danielle
collection PubMed
description The human salivary amylase genes display extensive copy number variation (CNV), and recent work has implicated this variation in adaptation to starch-rich diets, and in association with body mass index. In this work, we use paralogue ratio tests, microsatellite analysis, read depth and fibre-FISH to demonstrate that human amylase CNV is not a smooth continuum, but is instead partitioned into distinct haplotype classes. There is a fundamental structural distinction between haplotypes containing odd or even numbers of AMY1 gene units, in turn coupled to CNV in pancreatic amylase genes AMY2A and AMY2B. Most haplotypes have one copy each of AMY2A and AMY2B and contain an odd number of copies of AMY1; consequently, most individuals have an even total number of AMY1. In contrast, haplotypes carrying an even number of AMY1 genes have rearrangements leading to CNVs of AMY2A/AMY2B. Read-depth and experimental data show that different populations harbour different proportions of these basic haplotype classes. In Europeans, the copy numbers of AMY1 and AMY2A are correlated, so that phenotypic associations caused by variation in pancreatic amylase copy number could be detected indirectly as weak association with AMY1 copy number. We show that the quantitative polymerase chain reaction (qPCR) assay previously applied to the high-throughput measurement of AMY1 copy number is less accurate than the measures we use and that qPCR data in other studies have been further compromised by systematic miscalibration. Our results uncover new patterns in human amylase variation and imply a potential role for AMY2 CNV in functional associations.
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spelling pubmed-44981562015-07-15 Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes Carpenter, Danielle Dhar, Sugandha Mitchell, Laura M. Fu, Beiyuan Tyson, Jess Shwan, Nzar A.A. Yang, Fengtang Thomas, Mark G. Armour, John A.L. Hum Mol Genet Articles The human salivary amylase genes display extensive copy number variation (CNV), and recent work has implicated this variation in adaptation to starch-rich diets, and in association with body mass index. In this work, we use paralogue ratio tests, microsatellite analysis, read depth and fibre-FISH to demonstrate that human amylase CNV is not a smooth continuum, but is instead partitioned into distinct haplotype classes. There is a fundamental structural distinction between haplotypes containing odd or even numbers of AMY1 gene units, in turn coupled to CNV in pancreatic amylase genes AMY2A and AMY2B. Most haplotypes have one copy each of AMY2A and AMY2B and contain an odd number of copies of AMY1; consequently, most individuals have an even total number of AMY1. In contrast, haplotypes carrying an even number of AMY1 genes have rearrangements leading to CNVs of AMY2A/AMY2B. Read-depth and experimental data show that different populations harbour different proportions of these basic haplotype classes. In Europeans, the copy numbers of AMY1 and AMY2A are correlated, so that phenotypic associations caused by variation in pancreatic amylase copy number could be detected indirectly as weak association with AMY1 copy number. We show that the quantitative polymerase chain reaction (qPCR) assay previously applied to the high-throughput measurement of AMY1 copy number is less accurate than the measures we use and that qPCR data in other studies have been further compromised by systematic miscalibration. Our results uncover new patterns in human amylase variation and imply a potential role for AMY2 CNV in functional associations. Oxford University Press 2015-06-15 2015-03-18 /pmc/articles/PMC4498156/ /pubmed/25788522 http://dx.doi.org/10.1093/hmg/ddv098 Text en © The Author 2015. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Carpenter, Danielle
Dhar, Sugandha
Mitchell, Laura M.
Fu, Beiyuan
Tyson, Jess
Shwan, Nzar A.A.
Yang, Fengtang
Thomas, Mark G.
Armour, John A.L.
Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes
title Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes
title_full Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes
title_fullStr Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes
title_full_unstemmed Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes
title_short Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes
title_sort obesity, starch digestion and amylase: association between copy number variants at human salivary (amy1) and pancreatic (amy2) amylase genes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498156/
https://www.ncbi.nlm.nih.gov/pubmed/25788522
http://dx.doi.org/10.1093/hmg/ddv098
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