Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes.
Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes.
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DOI：
10.1093/hmg/ddv098
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发表时间：
2015-06-15
影响因子：
3.5
通讯作者：
Armour JA
中科院分区：
文献类型：
--
作者：
Carpenter D;Dhar S;Mitchell LM;Fu B;Tyson J;Shwan NA;Yang F;Thomas MG;Armour JA
人类唾液淀粉酶基因显示出广泛的拷贝数变异（CNV），最近的研究表明这种变异与对富含淀粉的饮食的适应有关，并与体重指数有关。在这项工作中，我们使用paramount比测试，微卫星分析，读取深度和fibre-FISH证明，人类淀粉酶CNV不是一个光滑的连续体，而是划分成不同的单倍型类。在含有奇数或偶数AMY 1基因单位的单倍型之间存在基本的结构区别，所述AMY 1基因单位继而与胰淀粉酶基因AMY 2A和AMY 2B中的CNV偶联。大多数单倍型都有一个AMY 2A和AMY 2B拷贝，并含有奇数个AMY 1拷贝;因此，大多数个体的AMY 1总数为偶数。相反，携带偶数个AMY 1基因的单倍型具有导致AMY 2A/AMY 2B的CNV的重排。阅读深度和实验数据表明，不同的人群海港这些基本单倍型类的比例不同。在欧洲人中，AMY 1和AMY 2A的拷贝数是相关的，因此胰腺淀粉酶拷贝数变异引起的表型关联可以间接检测为与AMY 1拷贝数的弱关联。我们表明，定量聚合酶链反应（qPCR）测定先前应用于AMY 1拷贝数的高通量测量是不准确的，比我们使用的措施，并在其他研究中的qPCR数据已被系统性的错误校准进一步损害。我们的研究结果揭示了人类淀粉酶变异的新模式，并暗示了AMY 2 CNV在功能关联中的潜在作用。
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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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Lazaridis, Iosif;Patterson, Nick;Mittnik, Alissa;Renaud, Gabriel;Mallick, Swapan;Kirsanow, Karola;Sudmant, Peter H.;Schraiber, Joshua G.;Castellano, Sergi;Lipson, Mark;Berger, Bonnie;Economou, Christos;Bollongino, Ruth;Fu, Qiaomei;Bos, Kirsten I.;Nordenfelt, Susanne;Li, Heng;de Filippo, Cesare;Pruefer, Kay;Sawyer, Susanna;Posth, Cosimo;Haak, Wolfgang;Hallgren, Fredrik;Fornander, Elin;Rohland, Nadin;Delsate, Dominique;Francken, Michael;Guinet, Jean-Michel;Wahl, Joachim;Ayodo, George;Babiker, Hamza A.;Bailliet, Graciela;Balanovska, Elena;Balanovsky, Oleg;Barrantes, Ramiro;Bedoya, Gabriel;Ben-Ami, Haim;Bene, Judit;Berrada, Fouad;Bravi, Claudio M.;Brisighelli, Francesca;Busby, George B. J.;Cali, Francesco;Churnosov, Mikhail;Cole, David E. C.;Corach, Daniel;Damba, Larissa;van Driem, George;Dryomov, Stanislav;Dugoujon, Jean-Michel;Fedorova, Sardana A.;Romero, Irene Gallego;Gubina, Marina;Hammer, Michael;Henn, Brenna M.;Hervig, Tor;Hodoglugil, Ugur;Jha, Aashish R.;Karachanak-Yankova, Sena;Khusainova, Rita;Khusnutdinova, Elza;Kittles, Rick;Kivisild, Toomas;Klitz, William;Kucinskas, Vaidutis;Kushniarevich, Alena;Laredj, Leila;Litvinov, Sergey;Loukidis, Theologos;Mahley, Robert W.;Melegh, Bela;Metspalu, Ene;Molina, Julio;Mountain, Joanna;Nakkalajarvi, Klemetti;Nesheva, Desislava;Nyambo, Thomas;Osipova, Ludmila;Parik, Jueri;Platonov, Fedor;Posukh, Olga;Romano, Valentino;Rothhammer, Francisco;Rudan, Igor;Ruizbakiev, Ruslan;Sahakyan, Hovhannes;Sajantila, Antti;Salas, Antonio;Starikovskaya, Elena B.;Tarekegn, Ayele;Toncheva, Draga;Turdikulova, Shahlo;Uktveryte, Ingrida;Utevska, Olga;Vasquez, Rene;Villena, Mercedes;Voevoda, Mikhail;Winkler, Cheryl A.;Yepiskoposyan, Levon;Zalloua, Pierre;Zemunik, Tatijana;Cooper, Alan;Capelli, Cristian;Thomas, Mark G.;Ruiz-Linares, Andres;Tishkoff, Sarah A.;Singh, Lalji;Thangaraj, Kumarasamy;Villems, Richard;Comas, David;Sukernik, Rem;Metspalu, Mait;Meyer, Matthias;Eichler, Evan E.;Burger, Joachim;Slatkin, Montgomery;Paeaebo, Svante;Kelso, Janet;Reich, David;Krause, Johannes
通讯作者：
Krause, Johannes
影响因子：
30.8
作者：
Perry, George H.;Dominy, Nathaniel J.;Stone, Anne C.
通讯作者：
Stone, Anne C.
影响因子：
9.8
作者：
Fellermann, Klaus;Stange, Daniel E.;Stange, Eduard F.
通讯作者：
Stange, Eduard F.
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C