Variation of BMP3 contributes to dog breed skull diversity.
Variation of BMP3 contributes to dog breed skull diversity.
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DOI：
10.1371/journal.pgen.1002849
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Ostrander EA
中科院分区：
文献类型：
--
作者：
Schoenebeck JJ;Hutchinson SA;Byers A;Beale HC;Carrington B;Faden DL;Rimbault M;Decker B;Kidd JM;Sood R;Boyko AR;Fondon JW 3rd;Wayne RK;Bustamante CD;Ciruna B;Ostrander EA
自驯化开始以来，家犬的颅面结构已经变形并辐射到人类的怪念头。通过开始定义品种头骨形状的遗传基础，我们可以阐明形态多样化的机制，同时提出一个框架，了解人类头部疾病。利用与博物馆标本测量的品种内关联作图，我们发现头骨形状至少受5个数量性状基因座（QTL）的调控。我们使用全基因组测序的详细分析揭示了BMP 3的错义突变。斑马鱼的验证研究表明，Bmp3在颅发育中的功能是古老的。我们的研究揭示了一个主要形态性状的犬QTL的因果变异。由于选择性繁殖的做法，现代狗显示出多种头部形状。品种，如哈巴狗和斗牛犬普及这些形态之一，被称为“brachycephaly”。短而向上的吻部，巨大而圆形的头部，以及下咬是短头犬的典型特征。在这里，我们将从博物馆头骨收集的表型与从狗收集的基因型相结合，并确定了与犬短头畸形相关的狗基因组的五个区域。在这些区域之一的精细定位揭示了基因BMP 3中的因果突变。bmp 3在调节颅骨发育中的作用在进化上是古老的，因为斑马鱼需要它的功能来产生正常的颅面形态。我们的数据开始揭露了育种者在不知不觉中创造和多样化狗的头骨形状的遗传机制。
Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait. As a result of selective breeding practices, modern dogs display a multitude of head shapes. Breeds such as the Pug and Bulldog popularize one of these morphologies, termed “brachycephaly.” A short, upward-pointing snout, a massive and rounded head, and an underbite typify brachycephalic breeds. Here, we have coupled the phenotypes collected from museum skulls with the genotypes collected from dogs and identified five regions of the dog genome that are associated with canine brachycephaly. Fine mapping at one of these regions revealed a causal mutation in the gene BMP3. Bmp3's role in regulating cranial development is evolutionarily ancient, as zebrafish require its function to generate a normal craniofacial morphology. Our data begin to expose the genetic mechanisms unknowingly employed by breeders to create and diversify the cranial shape of dogs.
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影响因子：
9.8
作者：
Boyko AR;Quignon P;Li L;Schoenebeck JJ;Degenhardt JD;Lohmueller KE;Zhao K;Brisbin A;Parker HG;vonHoldt BM;Cargill M;Auton A;Reynolds A;Elkahloun AG;Castelhano M;Mosher DS;Sutter NB;Johnson GS;Novembre J;Hubisz MJ;Siepel A;Wayne RK;Bustamante CD;Ostrander EA
通讯作者：
Ostrander EA
影响因子：
4.4
作者：
Quilez, Javier;Short, Andrea D.;Francino, Olga
通讯作者：
Francino, Olga
影响因子：
3.7
作者：
Bannasch D;Young A;Myers J;Truvé K;Dickinson P;Gregg J;Davis R;Bongcam-Rudloff E;Webster MT;Lindblad-Toh K;Pedersen N
通讯作者：
Pedersen N
影响因子：
10.5
作者：
Chikuda, H;Kugimiya, F;Kawaguchi, H
通讯作者：
Kawaguchi, H
影响因子：
7
作者：
Akey, JM;Zhang, G;Shriver, MD
通讯作者：
Shriver, MD