Mapping of the bovine spinal muscular atrophy locus to Chromosome 24
Mapping of the bovine spinal muscular atrophy locus to Chromosome 24
复制标题
牛脊髓性肌萎缩症基因座至 24 号染色体的定位
DOI：
10.1007/s00335-002-3024-3
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发表时间：
2003
期刊：
影响因子：
2.5
通讯作者：
M. Förster
中科院分区：
文献类型：
--
作者：
I. Medugorac;J. Kemter;I. Russ;D. Pietrowski;S. Nüske;H. Reichenbach;W. Schmahl;M. Förster
据报道，美国褐瑞士牛和美国褐瑞士牛与许多欧洲褐牛品种之间的高级回交中存在由常染色体隐性基因引起的脊髓性肌萎缩症（SMA）的遗传形式。牛SMA（bovSMA）与人SMA（SMA 1）具有显著的相似性。受影响的纯合子小牛还表现出进行性对称性无力和近端肌肉神经源性萎缩。这种情况的特征是严重的肌肉萎缩，四肢瘫痪，胸骨横卧作为神经性萎缩的结果。我们报告的定位的基因引起bovSMA之间的微卫星标记URB 031和端粒末端的牛染色体（Chr）24（BTA 24）的基因组间隔。连锁分析的一个复杂的谱系德国Braunvieh牛揭示了重组分数为0.06和三点lod得分为11.82。连锁和单倍型分析的结果使标记辅助选择bovSMA的基础上，四个微卫星标记最端粒的BTA 24到一个中等的准确性为89- 94%。到目前为止，该区域不是任何人类染色体片段的直向性，负责12个不同的疾病表型的常染色体神经病。我们的研究结果表明，BCL 2作为最有前途的位置候选基因引起bovSMA的发病抑制蛋白。我们的研究结果提供了一个有吸引力的动物模型，更好地了解人类形式的SMA和可能的抗凋亡协同作用的SMN-BCL 2聚集体在哺乳动物。
A hereditary form of spinal muscular atrophy (SMA) caused by an autosomal recessive gene has been reported for American Brown-Swiss cattle and in advanced backcrosses between American Brown-Swiss and many European brown cattle breeds. Bovine SMA (bovSMA) bears remarkable resemblance to the human SMA (SMA1). Affected homozygous calves also show progressive symmetric weakness and neurogenic atrophy of proximal muscles. The condition is characterized by severe muscle atrophy, quadriparesis, and sternal recumbency as result of neurogenic atrophy. We report on the localization of the gene causing bovSMA within a genomic interval between the microsatellite marker URB031 and the telomeric end of bovine Chromosome (Chr) 24 (BTA24). Linkage analysis of a complex pedigree of German Braunvieh cattle revealed a recombination fraction of 0.06 and a three-point lod score of 11.82. The results of linkage and haplotyping analysis enable a marker-assisted selection against bovSMA based on four microsatellite markers most telomeric on BTA24 to a moderate accuracy of 89–94%. So far, this region is not orthologous to any human chromosome segments responsible for twelve distinct disease phenotypes of autosomal neuropathies. Our results indicate the apoptosis-inhibiting protein BCL2 as the most promising positional candidate gene causing bovSMA. Our findings offer an attractive animal model for a better understanding of human forms of SMA and for a probable anti-apoptotic synergy of SMN-BCL2 aggregates in mammals.
影响因子：
9.8
作者：
E. Sobel;K. Lange
通讯作者：
E. Sobel;K. Lange
DOI：
10.1073/pnas.230364197
发表时间：
2000-11-21
影响因子：
11.1
作者：
Kerr, DA;Nery, JP;Hardwick, JM
通讯作者：
Hardwick, JM