U.S. Meat Animal Research Center (USMARC), Clay Center, Nebraska, USA.
PLoS One. 2013;8(2):e55490. doi: 10.1371/journal.pone.0055490. Epub 2013 Feb 11.
In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal's health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization-time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.
在绵羊中，小反刍动物慢病毒会导致一种无法治愈的、进行性的、淋巴增生性疾病，这种疾病影响着全球数以百万计的动物。这些病毒在美国被称为绵羊进行性肺炎病毒（OPPV），在其他地方则被称为 Visna/Maedi 病毒（VMV），它们会降低动物的健康、生产力和寿命。绵羊跨膜蛋白 154 基因（TMEM154）的遗传变异先前与美国绵羊的 OPPV 感染有关。与 K35 错义突变纯合的绵羊相比，编码谷氨酸（E）第 35 位的 TMEM154 祖先单倍型的绵羊以及 N70I 变体的任何一种形式的绵羊，其易感性都很高。我们目前的总体目标是对来自世界各地的绵羊进行 TMEM154 特征描述，以开发一种针对易感性降低的有效遗传检测方法。74 个品种中 TMEM154 E35 的平均频率为 0.51，表明在世界各地的大多数品种中都存在高度易感等位基因。对来自国际 75 个绵羊小组的全基因组序列的分析揭示了 TMEM154 包含的 62kb 区域中超过 1300 个以前未报告的多态性，并证实了最易感的单倍型分布在全球范围内。在 TMEM154 的信号肽（A13V）和细胞外结构域（E31Q、I74F 和 I102T）中发现了新的错义突变。开发了基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）检测方法来检测 TMEM154 中的这些突变以及之前报道的六个错义突变和两个缺失突变。在盲测中，对 499 只绵羊进行了 8 种最常见编码多态性的检测，其检出率为 99.4%，96.0%的动物被分配了配对的 TMEM154 单倍型（即二倍型）。高度易感的 TMEM154 等位基因的广泛分布表明，遗传检测和选择可能会提高受感染羊群的健康和生产力。
