Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed.
Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed.
复制标题
DOI：
10.1371/journal.pgen.1002462
复制
发表时间：
2012-01
期刊：
影响因子：
4.5
通讯作者：
Mellersh CS
中科院分区：
文献类型：
--
作者：
Forman OP;Penderis J;Hartley C;Hayward LJ;Ricketts SL;Mellersh CS
家犬（Canis familiaris）比任何其他物种分离更多的自然发生的疾病和表型变异，并已成为研究遗传性状遗传学的无与伦比的模型。我们使用了全基因组关联研究（GWAS），并对五只狗的DNA进行了有针对性的重测序，以同时绘制和识别两种不同遗传性疾病的突变，这两种疾病都影响一个品种，骑士查尔斯王猎犬。我们研究了阵发性跌倒（EF），一种阵发性运动诱发的运动障碍，以及表型不同的先天性干燥性角结膜炎和鱼鳞病样皮肤病（CKCSID），通常称为干眼卷曲综合征。EF的特征是运动引起的肌肉张力过高和姿势异常，通常发生在运动或兴奋期后。CKCSID是一种先天性疾病，表现为出生时存在粗糙的皮毛，在10-14天的眼睑张开时出现干燥性角结膜炎，随后在接下来的几个月内出现脚垫过度角化和指甲变形。我们对31例EF病例、23例CKCSID病例和38例对照组进行了GWAS，并分别在7号染色体（Praw 1.9×10−14; Pgenome = 1.0×10−5）和13号染色体（Praw 1.2×10−17; Pgenome = 1.0×10−5）上确定了EF和CKCSID的统计学相关信号。 我们对5只狗的EF和CKCSID疾病相关区域进行了重新测序，并确定了与EF相关的BCAN三个外显子的15，724 bp缺失和与CKCSID相关的FAM 83 H中的单碱基对外显子缺失。BCAN或FAM 83 H均未与任何其他物种中的等同疾病表型相关，因此证明了使用家犬在单一品种中同时研究一种以上疾病的遗传基础并平行鉴定多个新候选基因的能力。
The domestic dog (Canis familiaris) segregates more naturally-occurring diseases and phenotypic variation than any other species and has become established as an unparalled model with which to study the genetics of inherited traits. We used a genome-wide association study (GWAS) and targeted resequencing of DNA from just five dogs to simultaneously map and identify mutations for two distinct inherited disorders that both affect a single breed, the Cavalier King Charles Spaniel. We investigated episodic falling (EF), a paroxysmal exertion-induced dyskinesia, alongside the phenotypically distinct condition congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID), commonly known as dry eye curly coat syndrome. EF is characterised by episodes of exercise-induced muscular hypertonicity and abnormal posturing, usually occurring after exercise or periods of excitement. CKCSID is a congenital disorder that manifests as a rough coat present at birth, with keratoconjunctivitis sicca apparent on eyelid opening at 10–14 days, followed by hyperkeratinisation of footpads and distortion of nails that develops over the next few months. We undertook a GWAS with 31 EF cases, 23 CKCSID cases, and a common set of 38 controls and identified statistically associated signals for EF and CKCSID on chromosome 7 (Praw 1.9×10−14; Pgenome = 1.0×10−5) and chromosome 13 (Praw 1.2×10−17; Pgenome = 1.0×10−5), respectively. We resequenced both the EF and CKCSID disease-associated regions in just five dogs and identified a 15,724 bp deletion spanning three exons of BCAN associated with EF and a single base-pair exonic deletion in FAM83H associated with CKCSID. Neither BCAN or FAM83H have been associated with equivalent disease phenotypes in any other species, thus demonstrating the ability to use the domestic dog to study the genetic basis of more than one disease simultaneously in a single breed and to identify multiple novel candidate genes in parallel.
登录
查看更多内容
影响因子：
30.8
作者：
GEORGE, AL;CRACKOWER, MA;EBERS, GC
通讯作者：
EBERS, GC
影响因子：
1.6
作者：
Barnett, K. C.
通讯作者：
Barnett, K. C.
影响因子：
30.8
作者：
Karlsson, Elinor K.;Baranowska, Izabella;Lindblad-Toh, Kerstin
通讯作者：
Lindblad-Toh, Kerstin
影响因子：
4
作者：
Penderis, Jacques;Calvin, Jacqui;Mellersh, Cathryn S.
通讯作者：
Mellersh, Cathryn S.
影响因子：
7
作者：
McKenna, Aaron;Hanna, Matthew;DePristo, Mark A.
通讯作者：
DePristo, Mark A.