Identification of the single base change causing the callipyge muscle hypertrophy phenotype, the only known example of polar overdominance in mammals
Identification of the single base change causing the callipyge muscle hypertrophy phenotype, the only known example of polar overdominance in mammals
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DOI：
10.1101/gr.571002
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发表时间：
2002-10-01
期刊：
影响因子：
7
通讯作者：
Smith, TPL
中科院分区：
文献类型：
--
作者：
Freking, BA;Murphy, SK;Smith, TPL
一个小的遗传区域附近的端粒的绵羊染色体18先前被证明携带突变引起的calipyge肌肉肥大表型的绵羊。这种表型的表达是哺乳动物中唯一已知的父系极性超显性基因作用的情况。在已知基因型的动物中对围绕两个位置候选基因的区域进行测序。突变检测集中在一个近交系公羊callipyge表型假定继承的染色体片段相同的血统，除了突变的位置。为了支持这一假设，这只近交系公羊在210 Kb的序列上是纯合的，除了一个杂合的碱基位置。在分离callipyge基因座（COG）的多个家族中对这种单一多态性进行基因分型，与已知CLPG基因型的动物100%一致，并且对创始动物的后代是独特的。该突变位于小鼠、绵羊、牛和人类之间高度同源的区域，但不在任何先前鉴定的表达转录物中。一个实质性的开放阅读框架存在于绵羊序列周围的突变，虽然这个框架是不保守的物种。初步的功能分析表明，包含突变的序列是在绵羊胎儿肌肉中表达的新转录本的一部分，我们将其命名为CLPG 1。
A small genetic region near the telomere of ovine chromosome 18 was previously shown to carry the mutation causing the callipyge muscle hypertrophy phenotype in sheep. Expression of this phenotype is the only known case in mammals of paternal polar overdominance gene action. A region sur rounding two positional candidate genes was sequenced in animals of known genotype. Mutation detection focused on an inbred ram of callipyge phenotype postulated to have inherited chromosome segments identical-by-descent with exception of the mutated position. In support of this hypothesis, this inbred ram was homozygous over 210 Kb of sequence, except for a single heterozygous base position. This single polymorphism was genotyped in multiple families segregating the callipyge locus (COG), providing 100% concordance with animals of known CLPG genotype, and was unique to descendants of the founder animal. The mutation lies in a region of high homology among mouse, sheep, cattle, and humans, but not in any previously identified expressed transcript. A substantial open reading frame exists in the sheep sequence surrounding the mutation, although this frame is not conserved among species. Initial functional analysis indicates sequence encompassing the mutation is part of a novel transcript expressed in sheep fetal muscle we have named CLPG1.