Localization of canine brachycephaly using an across breed mapping approach.
Localization of canine brachycephaly using an across breed mapping approach.
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DOI：
10.1371/journal.pone.0009632
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发表时间：
2010-03-10
期刊：
影响因子：
3.7
通讯作者：
Pedersen N
中科院分区：
文献类型：
--
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
家犬表现出深刻的表型多样性，是简单和复杂性状遗传解剖的理想模式生物。然而，一些最有趣的表型是固定在特定的品种，因此不太听话的遗传分析，使用经典的分离为基础的映射方法。我们实施了一种跨品种作图方法，使用中等密度的SNP阵列，为感兴趣的表型仔细选择少量的动物和品种，以鉴定负责品种定义特征的遗传变异。使用来自多个品种的适度数量的受影响（10-30）和对照（20-60）样品，在使用三个先前定义的基因座的概念验证实验中鉴定正确的染色体分配;高尿酸尿、白色斑点和软骨发育不良。以类似的方式对狗中最引人注目的形态特征之一进行全基因组关联：短头型。虽然候选基因的方法的基础上可比的表型在小鼠和人类已被用于这一特点，致病基因仍然难以捉摸使用这种方法。从9个受影响的品种和13个对照品种的样本确定了强大的全基因组协会短头型头CFA 1。两个独立的数据集鉴定了相同的基因组区域。在相关区域的相对杂合性水平表明，它已受到选择性扫描，与它是一个品种定义形态特征一致。对该地区其他狗的基因分型证实了这种关联。到目前为止，狗品种的遗传结构主要是利用基因组范围内的分离性状的关联。这些结果表明，在强选择下的非分离性状同样易于使用小样本数进行遗传分析。
The domestic dog, Canis familiaris, exhibits profound phenotypic diversity and is an ideal model organism for the genetic dissection of simple and complex traits. However, some of the most interesting phenotypes are fixed in particular breeds and are therefore less tractable to genetic analysis using classical segregation-based mapping approaches. We implemented an across breed mapping approach using a moderately dense SNP array, a low number of animals and breeds carefully selected for the phenotypes of interest to identify genetic variants responsible for breed-defining characteristics. Using a modest number of affected (10–30) and control (20–60) samples from multiple breeds, the correct chromosomal assignment was identified in a proof of concept experiment using three previously defined loci; hyperuricosuria, white spotting and chondrodysplasia. Genome-wide association was performed in a similar manner for one of the most striking morphological traits in dogs: brachycephalic head type. Although candidate gene approaches based on comparable phenotypes in mice and humans have been utilized for this trait, the causative gene has remained elusive using this method. Samples from nine affected breeds and thirteen control breeds identified strong genome-wide associations for brachycephalic head type on Cfa 1. Two independent datasets identified the same genomic region. Levels of relative heterozygosity in the associated region indicate that it has been subjected to a selective sweep, consistent with it being a breed defining morphological characteristic. Genotyping additional dogs in the region confirmed the association. To date, the genetic structure of dog breeds has primarily been exploited for genome wide association for segregating traits. These results demonstrate that non-segregating traits under strong selection are equally tractable to genetic analysis using small sample numbers.
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影响因子：
2.6
作者：
Hédan B;Corre S;Hitte C;Dréano S;Vilboux T;Derrien T;Denis B;Galibert F;Galibert MD;André C
通讯作者：
André C
影响因子：
2.5
作者：
Kerns, JA;Newton, J;Barsh, GS
通讯作者：
Barsh, GS
影响因子：
4.5
作者：
Bannasch, Danika;Safra, Noa;Young, Amy;Karmi, Nili;Schaible, R. S.;Ling, G. V.
通讯作者：
Ling, G. V.
DOI：
10.1073/pnas.0402374101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Neff, MW;Robertson, KR;Pedersen, NC
通讯作者：
Pedersen, NC
DOI：
10.1073/pnas.0812297106
发表时间：
2009-02-24
影响因子：
11.1
作者：
Awano, Tomoyuki;Johnson, Gary S.;Coates, Joan R.
通讯作者：
Coates, Joan R.