Recurrent Rearrangements of Human Amylase Genes Create Multiple Independent CNV Series

Shwan, Nzar A. A.; Louzada, Sandra; Yang, Fengtang; Armour, John A.L.

doi:10.1002/humu.23182

Cited by 17 publications

(16 citation statements)

References 26 publications

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“…In parallel, we obtained independent duplicate copy number measurements by direct analysis of genomic DNA in 1,448 DNA samples from the 1958 Birth Cohort using ratio-based (PRT) methods (17), again demonstrating concordance with previous copy number distributions (Supporting Information Table S1) and the odd-even parity between AMY1 and AMY2A ( Figure 1B). The mean copy numbers found in 1958 Birth Cohort samples were 6.71 (range: 2-15) for AMY1, 2.0 (range: 0-5) for AMY2A, and 2.15 (range: 2-5) for AMY2B.…”

Section: Resultssupporting

confidence: 77%

No Evidence for Association of BMI with Salivary Amylase Gene Copy Number in the UK 1958 Birth Cohort

Shwan

Armour

2019

Obesity

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Objective In a 2014 publication, evidence was presented supporting the association of BMI with the copy number of the salivary amylase 1 (AMY1) gene, with an unprecedented effect size of −0.15 kg/m2 (SE 0.02) per copy of AMY1. Most well‐powered attempts to reproduce these findings have not been successful. However, because of different study designs, a significant association may still apply under restricted conditions such as in particular age groups. This study specifically tested the BMI‐AMY1 association at different age points in the same individuals using longitudinal BMI information from participants in the UK 1958 Birth Cohort study. Methods This study measured the AMY1 copy number by paralogue ratio tests in genomic DNA and by using array comparative genomic hybridization data. BMI data from 1958 Birth Cohort participants were available from eight different age points between 7 and 50 years. Results No evidence, even at nominal significance, was found for association of the AMY1 copy number with BMI at any age point in approximately 1,400 members of the 1958 Birth Cohort or in 2,835 people from two disease cohorts from the Wellcome Trust Case Control Consortium. Conclusions The results do not support an association between BMI and AMY1 copy number at any age point.

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Section: Resultssupporting

confidence: 77%

No Evidence for Association of BMI with Salivary Amylase Gene Copy Number in the UK 1958 Birth Cohort

Shwan

Armour

2019

Obesity

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“…But if AMY1 CNV does represent an adaptation to increased levels of starch in the human diet, at what point in evolutionary history did it occur, and why did it occur at that time? It has been suggested that it accompanied the development of agriculture [21,22,25,32,46,47], which occurred around 10,000 BC, but it is unlikely that such a major change in the genome could have occurred in such a short space of time. Furthermore, AMY1 CNV has been found in ancient hunter-gatherers, predating the introduction of agriculture [48,49].…”

Section: Evolutionary Drive For Cnv Within Amy1mentioning

confidence: 99%

“…Furthermore, we cannot accurately identify the exact temporal origin of AMY1 CNV, nor when cooking was widely adopted by human ancestors [30]. However, if the origin of AMY1 CNV predates the development of agriculture and postdates the widespread introduction of cooking, and may have been present in the first humans, it does not necessarily mean that it has conferred no selective advantage in modern human history [47]. It is still possible that high numbers of AMY1 copies were favoured in populations with starch-rich diets, and have been retained.…”

Section: Evolutionary Drive For Cnv Within Amy1mentioning

confidence: 99%

Human amylase gene copy number variation as a determinant of metabolic state

Elder

Ramsden

Burnett

et al. 2018

Expert Review of Endocrinology & Metabolism

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Humans have multiple genes encoding amylase that are broadly divided into salivary (AMY1) and pancreatic (AMY2) genes. They exhibit some of the greatest copy numbers of any human gene, an expansion possibly driven by increased dietary starch intake. Within the population, amylase gene copy number is highly variable and there is evidence of an inverse association between AMY1 copy number and BMI. Areas covered: We examine the evidence for the link between AMY1 and BMI, its potential mechanisms, and the metabolic effects of salivary and pancreatic amylase, both in the gastrointestinal tract and the blood. Expert commentary: Salivary amylase may influence postprandial 'cephalic phase' insulin release, which improves glucose tolerance, while serum amylase may have insulin-sensitizing properties. This could explain the favorable metabolic status associated with higher AMY1 copy number. The association with BMI is harder to explain and is potentially mediated by increased flux of undigested starch into the ileum, with resultant effects on short-chain fatty acids (SCFAs), changes in gut microbiota and effects on appetite and energy expenditure in those with low copy number. Future research on the role of amylase as a determinant of metabolic health and BMI may lead to novel therapies to target obesity.

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“…Copy number variations (CNVs), which include insertions, duplications, and deletions of genomic segments among individuals within species, are currently known to be 50 bps to several Mbps in length (Mills et al, 2011;Iskow et al, 2012;Zarrei et al, 2015). CNVs encompass such more nucleotides than other types of variations (e.g., SNPs and InDels) that they can result in more remarkable effects on the functional gene through perturbing the long-range regulation of gene expression, altering gene dosage or coding sequences, and creating new genes, consequently contributing to phenotypic variations (Redon et al, 2006;Innan and Kondrashov, 2010;Bickhart and Liu, 2014;Shwan et al, 2017). A growing body of evidence shows that CNVs are crucial drivers of phenotypic diversity, evolution, and adaptation in humans and animals (Perry et al, 2008;Iskow et al, 2012;Sudmant et al, 2015;Romero et al, 2017;Rinker et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Population Structure, and Selection Signatures Underlying High-Altitude Adaptation Inferred From Genome-Wide Copy Number Variations in Chinese Indigenous Cattle

Zhang

Wang

et al. 2020

Front. Genet.

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Copy number variations (CNVs) have been demonstrated as crucial substrates for evolution, adaptation and breed formation. Chinese indigenous cattle breeds exhibit a broad geographical distribution and diverse environmental adaptability. Here, we analyzed the population structure and adaptation to high altitude of Chinese indigenous cattle based on genome-wide CNVs derived from the high-density BovineHD SNP array. We successfully detected the genome-wide CNVs of 318 individuals from 24 Chinese indigenous cattle breeds and 37 yaks as outgroups. A total of 5,818 autosomal CNV regions (683 bp-4,477,860 bp in size), covering~14.34% of the bovine genome (UMD3.1), were identified, showing abundant CNV resources. Neighbor-joining clustering, principal component analysis (PCA), and population admixture analysis based on these CNVs support that most Chinese cattle breeds are hybrids of Bos taurus taurus (hereinafter to be referred as Bos taurus) and Bos taurus indicus (Bos indicus). The distribution patterns of the CNVs could to some extent be related to the geographical backgrounds of the habitat of the breeds, and admixture among cattle breeds from different districts. We analyzed the selective signatures of CNVs positively involved in high-altitude adaptation using pairwise Fst analysis within breeds with a strong Bos taurus background (taurine-type breeds) and within Bos taurus×Bos indicus hybrids, respectively. CNV-overlapping genes with strong selection signatures (at top 0.5% of Fst value), including LETM1 (Fst = 0.490), TXNRD2 (Fst = 0.440), and STUB1 (Fst = 0.420) within taurine-type breeds, and NOXA1 (Fst = 0.233), RUVBL1 (Fst = 0.222), and SLC4A3 (Fst=0.154) within hybrids, were potentially involved in the adaptation to hypoxia. Thus, we provide a new profile of population structure from the CNV aspects of Chinese indigenous cattle and new insights into high-altitude adaptation in cattle.

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Recurrent Rearrangements of Human Amylase Genes Create Multiple Independent CNV Series

Cited by 17 publications

References 26 publications

No Evidence for Association of BMI with Salivary Amylase Gene Copy Number in the UK 1958 Birth Cohort

No Evidence for Association of BMI with Salivary Amylase Gene Copy Number in the UK 1958 Birth Cohort

Human amylase gene copy number variation as a determinant of metabolic state

Population Structure, and Selection Signatures Underlying High-Altitude Adaptation Inferred From Genome-Wide Copy Number Variations in Chinese Indigenous Cattle

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