Grossi Anette B, Agerholm Jørgen S, Christensen Knud, Jensen Henrik E, Leifsson Páll S, Bendixen Christian, Karlskov-Mortensen Peter, Fredholm Merete
Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark.
Present address: Ellegaard Göttingen Minipigs A/S, Sorø Landevej 302, 4261, Dalmose, Denmark.
Acta Vet Scand. 2014 Dec 10;56(1):85. doi: 10.1186/s13028-014-0085-8.
Peripheral nerve sheath tumors (PNSTs) are frequently found in Danish cattle at slaughter. Bovine PNSTs share several gross and histopathological characteristics with the PNSTs in humans with heritable neurofibromatosis syndromes. The aim of the present study was to investigate a possible hereditary disposition to PNSTs in dairy cattle by statistical analysis performed on data from 567 cattle with PNSTs. Furthermore, a preliminary genome-wide association study (GWAS) was performed on DNA isolated from 28 affected and 28 non-affected Holstein cows to identify loci in the bovine genome involved in the development of PNSTs.
PNSTs were significantly more common in the Danish Holstein breed than in other breeds with 0.49% of Danish Holsteins slaughtered during an eight-year-period having PNSTs. PNSTs also occurred significantly more frequently in the offspring of some specific Holstein sires. Examination of three generation pedigrees showed that these sires were genetically related through a widely used US Holstein sire. The PNSTs included in GWAS were histologically classified as neurofibroma-schwannoma (43%), schwannoma (36%) and neurofibroma (21%) and derived from Holstein cows with multiple PNSTs. A single SNP on chromosome 27 reached genome-wide significance.
Gross and histological characteristics of bovine PNSTs are comparable to PNSTs in humans (schwannomatosis). Danish Holsteins are genetically disposed to develop PNSTs but the examined materials are insufficient to allow determination of the mode of inheritance.
外周神经鞘瘤（PNSTs）在丹麦屠宰牛中经常被发现。牛的PNSTs与患有遗传性神经纤维瘤病综合征的人类PNSTs具有一些大体和组织病理学特征。本研究的目的是通过对567头患有PNSTs的牛的数据进行统计分析，调查奶牛中PNSTs可能的遗传倾向。此外，对从28头患病和28头未患病的荷斯坦奶牛分离的DNA进行了初步的全基因组关联研究（GWAS），以确定牛基因组中与PNSTs发生相关的基因座。
PNSTs在丹麦荷斯坦品种中比在其他品种中明显更常见，在八年期间屠宰的丹麦荷斯坦牛中有0.49%患有PNSTs。PNSTs在一些特定荷斯坦公牛的后代中也明显更频繁地出现。对三代系谱的检查表明，这些公牛通过一头广泛使用的美国荷斯坦公牛存在遗传关系。GWAS中纳入的PNSTs在组织学上被分类为神经纤维瘤-施万细胞瘤（43%）、施万细胞瘤（36%）和神经纤维瘤（21%），并且来自患有多个PNSTs的荷斯坦奶牛。27号染色体上的一个单核苷酸多态性（SNP）达到了全基因组显著性。
牛PNSTs的大体和组织学特征与人类的PNSTs（神经鞘瘤病）相当。丹麦荷斯坦牛在遗传上倾向于发生PNSTs，但所检查的材料不足以确定遗传模式。
